Package for extended shelf life of liquid core catheters

ABSTRACT

Devices and methods are discussed directed to the use of a low profile laser ablation catheter for use in laser ablation removal of arterial plaque blockages to restore blood flow in the treatment of arteriovenous fistulas. Also discussed are devices and methods directed to packaging, long term storage and sterilization of liquid core ablation catheters.

RELATED APPLICATIONS

This application is a divisional of U.S. patent application Ser. No.14/515,435, filed Oct. 15, 2014, by J. Laudenslager et al., titled“Methods and Devices for Treatment of Stenosis of Arteriovenous FistulaShunts”, which claims priority under 35 USC 119(e) from U.S. ProvisionalPatent Application Ser. No. 61/891,830, filed Oct. 16, 2013, by J.Laudenslager et al., titled “Methods and Devices for Treatment ofStenosis of Arteriovenous Fistula Shunts”, the entirety of each areincorporated by reference herein.

BACKGROUND

Laser catheters and laser delivery systems in general have wide range ofapplications in the medical field. Such systems may be used to deliverlaser energy to desired sites of a patient's anatomy, and may beparticularly suitable for delivering laser energy to locations within apatient's body that allow for minimally invasive treatment of a varietyof indications using a variety of treatment modalities. Examples of somelaser treatment modalities include heating tissue, stimulating tissue,drug activation within a patient's tissue and ablation of tissue.

Laser catheters currently approved for ablating and clearing blockagesin human arteries may use a large single optical fiber, but may morecommonly use a bundle of multiple optical fibers having a silica core,or a core of some other solid transmissive material. Large single fiberstend to be very stiff and contraindicated for use in tortuous anatomyand bundles of multiple fibers tend to lack ablation efficiency at thedistal tip due to the gaps between adjacent fibers. This is particularlytrue for laser catheter systems that cut on contact. In addition, someindications for recanalization of blockages are particularly difficultto treat such that long term patency is maintained within a treatedvessel that has been opened. This is often the case where blockages inveins present soft grumous type plaque lesions that often also include alarge amount of soft thrombus.

What has been needed are fluid core waveguide based ablation cathetersthat are small and flexible enough to navigate a patient's vasculature,use biocompatible fluids, and are economical to manufacture. What hasalso been needed are such fluid core waveguide based ablation cathetersthat can be efficiently packaged and sterilized and maintain clinicalintegrity during a useful shelf life after shipment to an end user. Whathas also been needed are systems and methods suitable for treatinggrumous type lesions that improve long term patency of treated vessels.

SUMMARY

Some embodiments of a method of treating an arteriovenous fistula of apatient may include advancing a guiding device to the arteriovenousfistula, advancing a liquid core ablation catheter adjacent a blockagethat is disposed within or adjacent the arteriovenous fistula andguiding the distal end of the liquid core ablation catheter with theguiding device. The method embodiment may also include axially advancingthe liquid core ablation catheter through the blockage while emittingpulsed ultraviolet laser ablation energy from a distal end of the liquidcore ablation catheter thereby ablating the blockage and debulking theblockage until the blockage is axially traversed by the distal end ofthe liquid core ablation catheter.

Some embodiments of a method of treating an arteriovenous fistula of apatient include axially advancing a liquid core ablation catheterthrough a blockage that is disposed within or adjacent the arteriovenousfistula while emitting pulsed ultraviolet laser ablation energy from anactive emitting surface of a distal end of the liquid core ablationcatheter. In some cases, such a liquid core ablation catheter mayinclude an active emitting surface that is at least about 50 percent ofan area of the distal end of the liquid core ablation catheter. Themethod may also include ablating and debulking the blockage whileadvancing.

Some embodiments of a method of treating an arteriovenous fistula of apatient include emitting pulsed ultraviolet laser ablation energy from aXeCl excimer laser at a nominal output wavelength of about 308 nm and arepetition rate of less than about 100 Hz into an input end of anablation catheter and transmitting the pulsed ultraviolet laser ablationenergy through the ablation catheter. The method may also includeaxially advancing and guiding a distal end of the ablation catheterthrough a blockage that is disposed within or adjacent the arteriovenousfistula while emitting the pulsed ultraviolet laser ablation energy froman active emitting surface of the distal end of the ablation catheterwhile ablating and debulking the blockage. The method embodiment mayalso include treating the blockage with a drug eluting balloon catheterafter the distal end of the ablation catheter has traversed the blockageto improve long term patency of a lumen through the blockage.

Some package assembly embodiments to extend a shelf life of a liquidcore catheter may include a liquid core catheter comprising a coreliquid, a polymer spiral tube which includes an inner lumen filled witha storage liquid that is soluble in or miscible with the core liquid ofthe liquid core catheter and which is sealed at both ends to contain thestorage liquid in the inner lumen of the polymer spiral tube, and asealed pouch which is made of either metallized plastic orpolychlorotrifluoroethylene that acts as a hermetic seal for liquidsdisposed within the sealed pouch. The sealed pouch may also include ahermetically sealed inner volume with the polymer spiral tube and liquidcore catheter being disposed within the hermetically sealed innervolume.

Some embodiments of a liquid core ablation catheter may include acatheter tube having a fluoropolymer material and an internal coatingdisposed on an inner surface of the catheter tube. In some cases, theinternal coating may include an amorphous fluoropolymer having a lowindex of refraction of less than about 1.34. The liquid core ablationcatheter may also have an outer layer disposed on an outer surface ofthe catheter tube, the outer layer including polychlorotrifluoroethylenematerial that acts as a barrier to liquid diffusion out of an innerlumen of the catheter tube. Such prevention of liquid diffusion mayinclude prevention of water vapor diffusion. The liquid core ablationcatheter may also include a first solid window that seals the innerlumen at a first end of the catheter tube and a second solid window thatseals the inner lumen at a second end of the catheter tube.

Certain embodiments are described further in the following description,examples, claims and drawings. These features of embodiments will becomemore apparent from the following detailed description when taken inconjunction with the accompanying exemplary drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The drawings illustrate embodiments of the technology and are notlimiting. For clarity and ease of illustration, the drawings may not bemade to scale and, in some instances, various aspects may be shownexaggerated or enlarged to facilitate an understanding of particularembodiments.

FIG. 1 is a perspective view of a laser system embodiment including alaser and a disposable liquid core ablation catheter coupled to thelaser.

FIG. 2 is a perspective view of a laser system embodiment including areusable extension waveguide connected between a laser and a disposableliquid core ablation catheter.

FIG. 3 is an elevation view of an embodiment of a laser catheter systemincluding a liquid core ablation catheter disposed within a supportcatheter, the support catheter having a saline flush port.

FIG. 4 is an elevation view of the support catheter embodiment of FIG.2.

FIG. 5 is an elevation view of the liquid core ablation catheterembodiment of FIG. 2.

FIG. 6 is an enlarged elevation view in partial section of the laserconnector ferrule embodiment of FIG. 3 for use with a liquid coreablation catheter.

FIG. 7 is an enlarged view of the encircled portion 7 of the laserconnector ferrule embodiment of FIG. 6.

FIG. 8 is an elevation view in partial section of a distal portion ofthe liquid core ablation catheter embodiment of FIG. 3.

FIG. 9 is a transverse cross sectional view of the liquid core ablationcatheter of FIG. 8 taken along lines 9-9 of FIG. 8.

FIG. 10 is an elevation view in section of a distal portion of a liquidcore ablation catheter embodiment including a tapered metal housing.

FIG. 11 is a transverse cross sectional view of the liquid core ablationcatheter of FIG. 10 taken along lines 10-10 of FIG. 10.

FIG. 12 is a transverse cross sectional view of the liquid core ablationcatheter of FIG. 10 taken along lines 12-12 of FIG. 10.

FIG. 13 is a transverse cross section of the liquid core ablationcatheter embodiment of FIG. 5 taken along lines 13-13 of FIG. 5.

FIG. 14 is an enlarged view in section of the wall of the liquid coreablation catheter of FIG. 13 indicated by the encircled portion 14 inFIG. 13.

FIG. 15 is a transverse cross section view of an embodiment of a liquidcore ablation catheter with an eccentric guidewire lumen.

FIG. 16 is an elevation view of a distal portion of the liquid coreablation catheter embodiment of FIG. 15.

FIG. 17 is an elevation view of a distal portion of an embodiment of theliquid core ablation catheter embodiment of FIG. 15 having a taperedmetal housing disposed at a distal end thereof.

FIG. 17A is an end view of the distal end of the liquid core ablationcatheter of FIG. 17.

FIG. 18 is a transverse cross section view showing an embodiment of thesupport catheter of FIG. 4 and taken along lines 18-18 of FIG. 4.

FIG. 19 is an elevation view of a distal portion of the support catheterembodiment of FIG. 18.

FIG. 20 is an elevation view of a distal portion of a support catheterembodiment that includes a tapered distal portion.

FIG. 21 is an elevation view of a distal portion of a support catheterembodiment that includes an angled distal end.

FIG. 22 is an elevation view of a distal portion of a support catheterembodiment having an angled distal section configured for nutation of anablation catheter disposed therein.

FIG. 23 is an end view of the support catheter of FIG. 22.

FIG. 24 is a schematic representation of an annular area of ablationswept by the distal end of the liquid core ablation catheter whileundergoing nutation due to rotation of the angled support catheter ofFIG. 22.

FIG. 25 is a schematic representation of a circular area of ablationswept by the distal end of the liquid core ablation catheter whileundergoing nutation due to rotation of the angled support catheter ofFIG. 22.

FIG. 26 is a perspective view of a distal portion of an embodiment of amulti-lumen support catheter having two eccentric guidewire lumens.

FIG. 27 is an end view of the support catheter embodiment of FIG. 8A.

FIGS. 28 through 32 illustrate a method embodiment of an ablation methodembodiment.

FIG. 33 is a transverse section view of a patient's vessel illustratinga method embodiment of producing a larger lumen after a first pass of anablation catheter.

FIG. 34 is an elevation view in partial section of a patient's vessellumen and catheter system embodiment disposed therein.

FIG. 35 is an elevation view in partial section illustrating an ablationcatheter ablating additional material laterally adjacent the pilotlumen.

FIG. 36 is an elevation view in partial section illustrating creation ofan annular area of ablation of a vessel blockage by nutation of anablation catheter as shown in FIGS. 22-24.

FIGS. 37 through 43 illustrate schematic representations of variouscatheter manufacturing process embodiments.

FIG. 44 is an elevation view in section of a distal portion of a liquidcore ablation catheter embodiment including a tapered metal housing.

FIG. 45 is a transverse cross section view of the liquid core ablationcatheter of FIG. 44 taken along lines 45-45 of FIG. 44.

FIG. 46 is an enlarged elevation view in partial section of a laserconnector ferrule embodiment of FIG. 3 for use with a liquid coreablation catheter.

FIG. 47 is a transverse cross section view of the laser coupler of FIG.46 taken along lines 47-47 of FIG. 46.

FIG. 48 is a transverse cross section view of the laser coupler of FIG.46 taken along lines 48-48 of FIG. 46.

FIG. 49 is an enlarged view of the encircled portion 49 of the laserconnector ferrule embodiment of FIG. 46.

FIG. 50 is a transverse cross section view of the input optic couplerassembly of the laser coupler of FIG. 49 taken along lines 50-50 of FIG.49.

FIG. 51 shows a schematic representation of a packaging embodiment foruse with a liquid core ablation catheter.

FIG. 52 is a top view of an embodiment of a liquid core ablationcatheter disposed within a secondary liquid within an embodiment of acoiled polymer packaging tube which is supported by a cardboard supportsheet.

FIG. 52A is a transverse cross section view of the polymer packagingtube and liquid core ablation catheter of FIG. 52 taken along lines52A-52A of FIG. 52.

FIG. 53 is an exploded view of a package assembly embodiment includingthe coiled polymer packaging tube of FIG. 52 which may then be disposedwithin an interior volume of a sealed pouch which in turn may bedisposed within an interior volume of a rigid box.

FIG. 54 is an elevation view in section of an embodiment of theassembled package assembly of FIG. 53.

FIG. 55 is a schematic view of a patient's forearm showing an embodimentof an arteriovenous (AV) fistula formed between a vein and an artery ofthe patient's forearm by an arteriovenous graft.

FIG. 55A is a schematic view of a patient's forearm showing anembodiment of an arteriovenous fistula formed between a vein and anartery of the patient's forearm without the use of an arteriovenousgraft.

FIG. 56 shows the arteriovenous fistula embodiment of FIG. 5 with ablockage embodiment disposed within the arteriovenous fistula and thevein adjacent the arteriovenous fistula.

FIG. 57 is an enlarged view of the blockage embodiment of FIG. 56.

FIG. 58 illustrates the introduction of a guided laser ablation catheterbeing advanced within a vein towards the arteriovenous fistula.

FIG. 59 illustrates the laser ablation catheter of FIG. 58 being guidedby a guidewire and axially advanced through the blockage while emittingpulsed ultraviolet laser ablation energy from a distal end of the liquidcore ablation catheter and ablating and debulking the blockage.

FIG. 59A is a view of the arteriovenous fistula, the blockage, theablation catheter embodiment and the guidewire of FIG. 59 in transversecross section taken along lines 59A-59A of FIG. 59.

FIG. 60 illustrates the laser ablation catheter of FIG. 58 being guidedby a support catheter and axially advanced through the blockage whileemitting pulsed ultraviolet laser ablation energy from a distal end ofthe liquid core ablation catheter and ablating and debulking theblockage.

FIG. 61 is a view of the arteriovenous fistula, the blockage, theablation catheter embodiment and the support catheter of FIG. 60 intransverse cross section taken along lines 61-61 of FIG. 60.

FIG. 62 is an elevation view of an embodiment of a support catheterwhich includes a deflectable distal section.

FIG. 63 shows the enlarged view of the arteriovenous fistula of FIG. 57after ablation and debulking of the blockage by the ablation catheterembodiment as shown in FIG. 59 or 60.

FIG. 64 shows the enlarged view of the arteriovenous fistula of FIG. 57during treatment of the blockage in the arteriovenous fistula by a drugeluting angioplasty balloon embodiment.

FIG. 65 shows the enlarged view of the arteriovenous fistula of FIG. 57during treatment of the blockage in the vein adjacent the arteriovenousfistula by a drug eluting angioplasty balloon embodiment.

FIG. 66 illustrates a patent lumen through the blockage shown in FIG. 57after treatment of the arteriovenous fistula.

DETAILED DESCRIPTION

As discussed above, laser catheters and laser delivery systems ingeneral have wide range of applications in the medical field. Suchsystems may be used to deliver laser energy to desired sites of apatient's anatomy, and may be particularly suitable for delivering laserenergy to locations within a patient's body that allow for minimallyinvasive treatment of a variety of indications using a variety oftreatment modalities. Examples of some laser treatment modalitiesinclude heating tissue, stimulating tissue, drug activation within apatient's tissue and ablation of tissue or other organic material withina patient. Some examples of clinical indications for laser treatment mayinclude laser atherectomy. One drawback of some current laser systems isthe cost of the systems and devices used to deliver the laser energy,particularly with regard to those components that are designated assingle use products. Liquid core catheter embodiments 22, as shown inFIG. 3, may generally be considerably less expensive than a silica fiberoptic based catheter and may also have less dead space in the cuttingarea at the distal end of the catheter. The reduced dead space (thatdistal surface area that is not emitting laser energy) may be animportant feature for ablation of blockages in arteries and for theability of the catheter to cross a lesion in a patient's vessel.

FIGS. 1-27 show a laser ablation system embodiment 8 that includes alaser energy source 10 including a housing 12, a power cord 14, anactivation footswitch 16, a control panel 18 and an output coupler 20. Aliquid core ablation catheter 22 has a laser coupler 24 which isdisposed at a proximal end 30 of the ablation catheter 22 and which iscoupled to the output coupler 20 of the laser source 10. The ablationcatheter 22 is disposed within an inner lumen 28 (as shown in FIG. 18)of a support catheter 26 which may be used to guide or support theablation catheter 22 within a body lumen of a patient. The supportcatheter 26 includes a Y-adapter 32 coupled to a proximal end 30thereof. The liquid core ablation catheter 22 is disposed within andpasses through a central lumen (not shown) of the Y-adapter 32 as well.The support catheter 26 and ablation catheter 22 each may have aradiopaque marker 31 disposed at a respective distal end thereof. Aworking length of the liquid core ablation catheter 22 may include thelength inside the patient's body between the access point and the targetlesion site and the length outside the body necessary to couple or passthrough the Y connector 32. An additional length may be needed to couplethis working distance of about 90 cm to about 120 cm to the laser source10 in some cases. If a laser source is large and located away from thepatient, an additional length of waveguide may be necessary. Some lasercatheter embodiments may be about 2 meters to about 3 meters long insome cases. In some cases, the laser source 10 of the laser system 8 mayinclude a XeCl excimer laser which produces high energy pulses at awavelength of about 308 nanometers, however, other high energy pulsedultraviolet laser sources may be used. Some laser source embodiments 10may have a pulse width of less than about 50 nanosec and a repetitionrate of up to about 100 Hz. Some such laser source embodiments 10 may becapable of producing about 20 to about 100 mJ/pulse.

For some embodiments, the laser system 8 may also include an aimingdiode (not shown) for applications where locating the distal tip 34 ofliquid core ablation catheter 22 visually may be desirable. For someembodiments, a red color diode light source (not shown) may be used.This red diode wavelength may have a wavelength that is configured topenetrate some tissue types and may provide visibility of the distal tip34 of the liquid core ablation catheter 22 and its position in the leganatomy. The red diode light source may be located in the laser coupler20 of the laser source 10 and coupled to the liquid core ablationcatheter 22 by turning mirror or beam splitter (not shown) in somecases.

Since some ablation catheters 22 are generally disposable or single useonly, the long 2-3 meter working length may be costly. For embodimentsdiscussed herein, a robust liquid filled extension waveguide 36 forcoupling from the laser source 10 to the single use disposable liquidcore ablation catheter 22 may be used outside a patient's body and bedesigned to last for multiple uses. Such an optional extension waveguide36, as shown in FIG. 2, may be used to connect the laser source 10 ofthe laser system 8′ to a single-use liquid core ablation catheter 22 andhave a length suitable to reach from the laser source 10 to the patienttable (not shown). In some cases, the extension waveguide 36 may have alength of about 75 cm to about 300 cm, more specifically, about 75 cm toabout 150 cm. The extension waveguide 36 may also be configured tocontain a higher IR liquid core fluid than disposable liquid coreablation catheter embodiments 22 because it is generally disposed andused outside the patient's body and is not subject to some of the samedesign constraints as discussed above. As such, core liquids that have ahigher IR may be used that may not be biocompatible in some cases.

With regard to laser system embodiments 8 such as those shown generallyin FIGS. 1 and 2, there are some features of the ablation cathetersystem 27, which includes the liquid core ablation catheter 22 andsupport catheter 26, shown in more detail in FIG. 3, that may bedesirable or even necessary in some cases to function as desired. Theliquid core ablation catheter 22, as shown in more detail in FIGS. 3, 5,6, 8 and 10, includes a multi-layer catheter tube 38 having a lowprofile to fit inside particular blood vessels, which may have innerluminal diameters or inner transverse dimensions that vary in size fromabout 2 mm to about 6 mm. The wall thickness of the multi-layer cathetertube 38 of the liquid core ablation catheter 22 may be thin relative toa transverse dimension of the liquid core 40, as shown in FIG. 13, toinsure flexibility and to minimize the “dead space” between an outerdistal surface 42 of the output window 82 (shown in FIG. 8) which emitstissue ablating energy and an outer dimension of the multi-layercatheter tube 38 which does not emit tissue ablating energy. Thenon-emitting wall of the catheter tube 38 forms the “dead space” thatdoes not contribute to tissue cutting or ablation. As such, the ablationcatheter 22 has a large fraction of cutting area relative to the overallarea of the distal tip or surface of the ablation catheter. This may beachieved by having a multi-layer catheter tube 38 with a thin wallthickness as shown in FIG. 13.

For some embodiments, the multi-layer catheter tube 38 of the ablationcatheter 22 is flexible enough to maneuver around bends in a patient'sartery without kinking yet be stiff enough to be able to push theablation catheter 22 through the vessel while ablating blockages. Insome cases, the catheter tube 38 is able to be torqued and rotated atthe distal end of the catheter tube 38 from a proximal portion 39 of thecatheter tube 38 that extends outside the patient's body.

In some cases, the core fluid 40 used in the ablation catheter 22 istransparent in the ultraviolet laser energy wavelengths and may be abiocompatible fluid in case of accidental leakage from the catheter 22.In addition, the configuration of fluid core ablation catheter 22 may becapable of transmitting high power pulses above a tissue ablationthreshold in the ultraviolet wavelength range preferably with pulsewidths shorter than 50 nsec and at repetitions rates of up to 100 Hz inorder to achieve the desired results in some cases. For someindications, the liquid core ablation catheter 22 may be designed forsingle use only but may also have a long shelf life after sterilizationof typically one year or more for use in a clinical setting. Therefore,the core liquid 40 disposed in the inner lumen 46 of the ablationcatheter 22 should not diffuse out of the thin wall multi-layer cathetertube 38 of the catheter system 27, as shown in FIG. 3, over this type oftime period for some embodiments. Also, for some embodiments, thematerials of the multi-layer catheter tube 38 may be sterilizablewithout significant degradation or degradation that would render theablation catheter 22 unusable. Gamma or X-ray sterilization may be idealin some situations and may be useful in order to ensure that any fluid,such as liquid water used for a transmissive core, inside the ablationcatheter is sterilized.

For some embodiments, the transmission of laser energy through theliquid core ablation catheter 22 is high enough to enable a relativelysmall laser source to be used for the laser system 8 in order to savecost. For some indications, the ablation catheter 22 allows sufficienttransmission to achieve a minimum output energy per pulse to ablatediffering arterial plaque types or any other organic material within apatient's body. In some cases, such a minimum output energy may rangefrom about 4 milli-Joules/mm² (mJ/mm²) to about 14 mJ/mm² for a XeCllaser at a wavelength of about 308 nanometers (nm) and an approximatepulse width of about 10 nanoseconds (nsec) in some cases. Longer 308 nmlaser pulses of about 100 nsec may have slightly higher ablationthresholds for the same tissue types. As such, a fluid for the core ofthe liquid filled waveguide may transmit high power and high pulseenergy ultraviolet excimer laser pulses in some cases and may bebiocompatible for insertion into human arteries. Pure water and normalsaline (0.9% NaCl aqueous solution) are highly transparent and arebiocompatible but they both have very low indices of refraction (IR)compared to the IR of most polymer tubing materials used in liquidwaveguide catheters. For example, at a temperature of about 20 degreesC., water has an IR of about 1.333 in the visible wavelength region andnormal saline has an IR of about 1.335. Teflon® fluorinated ethylenepropylene (FEP) tubing may have an IR in the visible range of light ofabout 1.338 which may be too high to produce an effective waveguideusing water or saline for some ablation catheter embodiments 22. This isbecause the IR of the inner luminal layer 48 of the catheter tube 38 asshown in FIG. 14, must be less than the IR of the fluid core 40 toachieve total internal refraction of laser energy being guided by theliquid core ablation catheter.

Embodiments of the catheter system 27 may be used for navigation withinthe tortuous anatomy of a patient's vasculature may include a multilayerdesign or designs. In some cases, a central catheter tubing core 50 mayoptionally be braided with a metal wire or ribbon 52 and this portionmay have an over jacket 54 as shown in FIG. 13. This type of design maybe used for applications that require high torque, burst pressureresistance, pushability, steerability and kink resistance. The physicalcharacteristics of such a braided catheter embodiment 27, as shown inFIG. 3, may be varied by using different durometer values for theplastic tubing of the catheter body and by varying the pitch andthickness for the metal braid. This basic design concept may be appliedto the unique characteristics of liquid core ablation catheterembodiments 22.

In some cases, the laser ablation catheter system 27 includes a guidingdevice or other suitable means of guidance of the ablation catheterthrough a vessel lumen or blockage thereof, such as an arterialblockage. Guidewire 56, as shown in FIG. 31, which is disposed in aconcentric or eccentric position within a vessel 119 may be used in somecases as a guiding device and may pass through one or more guidewirelumens, such as guidewire lumen 58 of the liquid core ablation catheterembodiment 22′ as shown in the embodiments of FIGS. 15 and 16. Theablation catheter 22′ includes an eccentric guidewire lumen 58 disposedalong an outer surface of the ablation catheter 22. The guidewire lumenmay have a distal port disposed proximally from a distal end of theablation catheter 22′ by at least about 5 mm. The guidewire lumen 58 mayhave a longitudinal length of at least about 10 cm. Support catheterembodiments 26′″ including one or more guidewire lumens such as the twoguidewire lumens 60 and 62, as shown in the embodiments of FIGS. 26 and27, may also be used to guide and support the ablation catheter.

In addition, straight support catheters 26 as shown in FIG. 19 or angledsupport catheters 26′ as shown in FIG. 21, may be used as a guidingdevice for guiding a liquid core ablation catheter 22 through restenosedstents in that the stent itself may serve as a guide to maintain adesired position of the distal end of the ablation catheter 22 withinthe patient's anatomy or prevent the ablation catheter 22 from causingan arterial wall perforation. Some support catheter embodiments mayinclude a tapered support catheter embodiment 26″, angled supportcatheter embodiment 26′ or profiled support catheter embodiment as shownin FIGS. 20 and 21 to help center the liquid waveguide ablation catheter22 remain in the vessel lumen 118 during use as shown for example inFIGS. 28-32. The angled support catheter embodiment 26′ as shown in FIG.21, may have an angled distal tip section 57′ with a discharge axis 57disposed at an angle, indicated by arrow 59, with respect to a nominallongitudinal axis 61 of the support catheter 26′. For some embodiments,the angle 59 of the discharge axis of the support catheter 26′ may beabout 5 degrees to about 45 degrees, more specifically, about 10 degreesto about 30 degrees. In other cases, a straight support catheter with ameans to angle or otherwise transversely deflect the tip in one or moredirections or axes, as shown in FIG. 62, can be used to deflect the tipfrom a straight configuration to an angled deflected configurationhaving an angle 59 of up to a 45 degree angle for proper positioning ofthe ablation catheter cutting tip. An example of such a support catheterhaving a deflecting tip or distal section may include a UniversalDeflectable Guide Catheter, model 01415 manufactured by BioCardiaCorporation located at 125 Shoreway Road, Suite B, San Carlos, Calif.

In addition, an angled support catheter embodiment 26′, as shown inFIGS. 22-25, may be rotated about its longitudinal axis, as shown byarrow 65 in FIG. 22, over an ablation catheter, such as liquid coreablation catheter 22, which extends distally therefrom. Such rotation ofan angled support catheter 26′ with a deflected distal section mayresult in orbiting or nutation of the distal tip of ablation catheter 22during the ablation process, i.e. during emission of ablation energysuitable for tissue ablation from the distal end of the liquid coreablation catheter 22. This nutation of the ablation energy emittingsurface of the liquid core ablation catheter 22 may produce a band orannulus of ablation or tissue removal as shown in FIG. 24. Such aprocess is also illustrated in the elevation view of a tissue ablationprocess shown in FIG. 36. The band or annulus of ablation produced bysuch and configuration and method may be suitable to create a largerneo-lumen or passage through a lumenal blockage, obstruction orconstriction than would be possible by pushing the same liquid coreablation catheter 22 directly through the obstruction or constriction ina straight line. Although FIGS. 24 and 36 illustrate a band or annulusof ablation carried out by nutation of the support catheter 26′ aboutthe liquid core ablation catheter 22, a circular area of ablation mayalso be generated for rotations with lesser nutation magnitudes as shownin FIG. 25. In such cases, some portion or portions of the emittingsurface of the distal end of the liquid core ablation catheter 22 wouldbe disposed over a center of the neo-lumen being ablated into theobstructive tissue. In such cases, the neo-lumen may still besubstantially larger than an outer surface of the emitting surface orouter transverse dimension of the liquid core ablation catheter 22. Insome instances, the angled distal section 57′ of the angled supportcatheter 26′ may have a length, as shown by arrow 63 in FIG. 22, ofabout 5 mm to about 50 mm, more specifically, about 5 mm to about 15 mm.In some cases, a discharge angle as indicated by arrow 59′ in FIG. 22may be about 3 degrees to about 10 degrees.

In some cases, the numerical aperture of a liquid core ablation catheter22 may be above a certain minimum value in order to prevent losses inthe catheter, particularly due to bending of the catheter. The numericalaperture of the liquid core ablation catheter 22 depends to a largeextent on the difference between the IR of the core liquid 40 and the IRof an inner luminal layer 48 of the multi-layer catheter tube 38. Theinner luminal layer 48 is a tubular layer of material or materials ofthe catheter tube 38 which surrounds the core liquid 40 within theliquid core ablation catheter 22. The inner luminal surface 64 (shown inFIG. 14) of the inner luminal layer 48 is the surface that contacts thecore liquid 40. It is the interface between the core liquid 40 and theinner luminal layer 48 that may be configured to generate total internalrefraction of laser light disposed and propagating within the coreliquid 40. As such, in some cases, the IR of the core liquid 40 shouldbe greater than an IR of the inner luminal layer 48 of the catheter tube38 by at least about 0.02.

The inner luminal layer 48 of the catheter tube 38 may also betransparent or substantially transparent to the wavelength of laserenergy being transmitted through the core liquid 40. This may beparticularly desirable because the U.V. radiation refracting at the coreliquid 40 inner luminal layer 48 interface may extend into the innerluminal layer 48 (and possibly beyond the inner luminal layer 48 of themulti-layer catheter tube 38) by a distance of about several wavelengthsduring the refraction process. When the refracted light extends into theinner luminal layer 48 (or any other subsequent layers of themulti-layer catheter tube 38 such as the base layer tube 50 as shown inFIG. 14) during the refraction process it may be strongly absorbed ifthe material of the inner luminal layer 48 is not transparent orsubstantially transparent to the wavelength and energy density of therefracted light. This means that many materials may be incompatible foruse as an inner luminal layer 48 of the multi-layer catheter tube 38 ofthe liquid core ablation catheter 22, particularly for embodiments usinga core liquid 40 of water or normal saline.

In view of the foregoing, inner luminal layer embodiments 48 may begenerated by coating an internal surface 66 of the base layer 50, asshown in FIG. 14, of a multi-layer catheter tube 38 made from commoncatheter materials with a film of material having an IR of less thanabout 1.33. As discussed above, it may be important for such a coatingmaterial to be transparent or substantially transparent to theultraviolet wavelength used in the corresponding catheter. In addition,the inner luminal layer 48 may also have a sufficient wall thickness toretain the high power U.V. laser energy and prevent substantial lossesthrough the inner luminal layer 48 to those layers of the catheter tube38 surrounding the inner luminal layer 48 as for some embodiments, thesurrounding tubular layers may include materials which absorb the U.V.laser energy and may be damaged or destroyed by it.

Certain amorphous fluoropolymers may be used as coatings having a low IRrelative to some core liquids 40 and thus may be used for the generationof an inner luminal layer 48 of catheter tubes 38. DuPont® Corporationlocated in Wilmington Del. has developed certain coatings including, inparticular, fluorinated (ethylenic-cyclo oxyaliphatic substitutedethylenic) copolymer (Teflon AF®) which is a family of amorphousfluoropolymers based on copolymers of2,2-bistrifluoromethyl-4,5-difluoro-1,3-dioxole (PDD) andtetrafluoroethylene (TFE). According to DuPont, the principle differencebetween the various grades of Teflon AF® is based solely on the relativeamounts of TFE to PDD in the polymer chain. Teflon AF® polymers have thelowest index of refraction of any known polymer and are substantiallytransparent to light, even at U.V. wavelengths making these materialssuitable as low index coatings for waveguide applications. In somecases, these amorphous fluoropolymers may be formulated with differentIRs. Teflon AF 2400® has a TFE to PDD ratio of about 11:89 and aparticularly low IR of about 1.29 in the visible light wavelength range.Teflon AF 1601® has a TFE to PDD ratio of about 36:65 and an IR of about1.31 at the visible light wavelength range. Either of these formulationsmay be used to form an inner luminal layer 48 of the multi-layercatheter tube 38 of the ablation catheter 22. It should be noted thatthe IR of these fluorinated polymers as well as the IR of water andnormal saline, increase in value for UV wavelengths relative to valuesfor light in the visible wavelength range.

We have measured the transmission of 308 nm laser pulses through bothwater and saline filled tubes of uncoated Teflon® FEP and observed thatthe light was lost in the first foot of the tube. Pulses having awavelength of about 308 nm may be readily transmitted through a meterlong FEP tube filled with the same fluids when the tube was lined withTeflon AF 1601®. Therefore, in the UV the IR difference between water orsaline and the Teflon AF 1601® or Teflon AF 2400® appears to besufficient for total internal refraction and high transmission of shortpulse laser energy having a pulse width of less than about 50 nsec and awavelength of about 308 nm.

These amorphous fluoropolymers discussed above may be soluble inselected solvents to facilitate coating processes. In some cases, theseamorphous fluoropolymer coatings adhere best to fluorocarbon polymersbut not very well to other plastic types. As such, when using anamorphous fluorinated polymer material for an inner luminal layer 48 ofthe embodiments herein, the choice of suitable materials for theremaining layers of the catheter tube 38 may be limited. These and otherproperties of the amorphous fluorinated polymer materials may alsocreate difficulties for construction of suitable catheter tubes 38utilizing amorphous fluorinated polymer materials for the inner luminallayer. For example, Teflon AF 2400® which has an IR of about 1.29 isgenerally produced in a 1% solution which may be too dilute to achieve asufficient coating thickness to confine U.V. laser energy to the coreliquid 40 and inner luminal layer 48. Teflon AF 1601® withconcentrations up to about 18% may be used to produce a coating for aninner luminal layer 48 with sufficient thickness to confine U.V. laserenergy at 308 nm wavelength and with an IR of about 1.31.

Teflon® FEP tubes may not be as suited for use with liquid filled laserwaveguides 22 in some cases because water and aqueous solutions ofsaline over time may diffuse out of the FEP tube in low humidityenvironments. As an example, we filled a thick wall tube of Teflon® FEPwith water, sealed the ends and placed it in an oven at 50 degrees C.and saw bubble formation within 10 days. In some cases, this diffusionof water might be prevented by placing the FEP water filled tube in aplastic enclosure which also contains water. For example, the finishedFEP liquid filled ablation catheter can be packaged in a spiral plastictube filled with a second liquid that may be the same as the liquiddisposed within the core of the liquid filled ablation catheter, or asecond liquid that is soluble in or miscible with the liquid that isdisposed within the core of the liquid filled ablation catheter. In somecases, the second liquid may include water or a saline solution. Thespiral plastic tube may be sealed at both ends for long storage shelflife. This spiral package may then be sealed in a hermatic pouch formedof either PCTFE or metalized plastic material as shown in FIGS. 52-54and discussed in more detail below. The entire package containing thecatheter may then be sent for gamma sterilization to sterilize all thefluid contained in the catheter and spiral. In some cases, catheters 22may be placed in an oven at about 50 degrees C. to about 60 degrees C.for several months to perform accelerated lifetime testing to simulate aone year shelf life. Therefore, in some cases, it may be desirable forthe multi-layer catheter tube 38 of the ablation catheter 22 to not havea high permeability for water transfer at oven temperatures of about 50degrees C. to about 60 degrees C. to qualify as a medical catheter forlong shelf life in some cases. In addition, for some applications, thetubing material or materials of the multi-layer catheter tube 38 and/orsupport catheter 26 should be suitable for sterilization with gammaradiation or x-rays without significant degradation. Teflon® FEP isgenerally not as suitable for high levels of gamma radiationsterilization.

Another disadvantage with using an FEP tube liner may be that thehardness shore durometer of about 55 D is about half that of PCTFE whichmay have a shore hardness of about 85 D to about 95 D. When the FEPliner is thin and has a low durometer then there may be an impression ofthin elements of an optional braid material 52 used on an outsidesurface 68 (shown in FIG. 14) of a base tube 50 of the multi-layercatheter tube 38 to transfer into the inner luminal surface 64 of theinner luminal layer 48 which may cause the light to be scattered out ofthe tube. Also, when an ablation catheter 22 is placed in the Y adapter32 and a corresponding hemostatic valve thereof, the valve maycompresses a low durometer ablation catheter embodiment 22, distort thewall structure of the ablation catheter and hinder transmission of lighttherethrough.

We have found that polychlorotrifluoroethylene, PCTFE, has one of thelowest diffusion rates for water compared to other polymer plastics, andcan be coated with Teflon AF® solutions and can also be sterilized usingradiation. We filled a thin wall PCTFE tube with water and sealed theends of the tube and placed the sealed assembly in an oven at 60 degreesC. for one month. No diffusion of the water in the PCTFE tube wasapparent even after the one month dwell time in the oven. As such, PCTFEmay be used in some cases for certain layers of the multi-layer cathetertube 38. In fact, a liquid filled UV ablation catheter made of FEP orsimilar material with a low index coating applied can be over extrudedwith a thin layer of PCTFE to provide an alternative or cumulative meansfor providing a water barrier or vapor barrier for other liquids forlong term shelf life storage.

The higher durometer for PCTFE of about 90 D even with thin walls ofabout 0.002″ may provides extra stiffness that resists penetration ortransfer of a braid pattern onto an inner luminal surface 64 of theinner luminal layer 48 a liquid core ablation catheter 22. This higherdurometer may also add stiffness and pushability to the multi-layercatheter tube 38, but might kink easily in some cases without theoptional metal braid 52. PCTFE tubing does have a draw back in that themaximum working temperature of the material may be about 125 degrees C.in some cases. For some embodiments, the ablation catheter 22 mayinclude a multi-layer catheter tube 38 an outer layer or over-jacket 54,as shown in FIGS. 13 and 15, having a lower hardness durometer of about65 D to about 75 D, more specifically, about 70 D. In some cases, theouter layer or over-jacket layer 54, as shown in FIG. 13, may have to beprocessed at a temperature level where the PCTFE wall of the base tubeis not compromised. This may have the effect of substantially limitingthe choice of materials and processing methods for the over-jacket 54for the multi-layer catheter tube 38 of the liquid core ablationcatheter 22.

There are several options for forming the inner luminal layer 48 of themulti-layer catheter tube 38 from an amorphous Teflon AF® or othersuitable amorphous fluoropolymer on the inside of a base tube 50, suchas a PCTFE or FEP base tube 50. One method of creating such an innerluminal layer 48 includes using a solution of Teflon AF® dissolved atpercentages of about 1% to about 18% Teflon AF® solids in a suitablesolvent such as Fluorinert solvent. One type of Fluorinert is aperfluorcarbon made by 3M Company under the description FC-40. TheFluorinert solvent may be offered in various formulations that havediffering boiling points. In some cases, a Fluorinert solvent having aboiling point of about 155 degrees C. may be used for the processesdiscussed herein.

One or more coatings may be applied to the inside of the PCTFE tube andthe solvent may then be evaporated off to leave a thin layer solid filmof low IR of Teflon AF® of about 5 microns to about 50 microns thick,more specifically, about 5 microns to about 20 microns thick. VariousTeflon AF® layers with differing IRs and concentrations may be appliedor mixtures of differing solutions may be applied in a single mixedlayer. Examples of amorphous coatings with low indices of refraction mayinclude Teflon AF 1601®, Teflon AF 2400®, Cytop® manufactured by AsahiGlass Company located in Japan, and Hyflon AD 40® or Hyflon AD 60® madeby Solvay Solexis Company located in Italy. Any of these amorphousfluoropolymers may be mixed with a high boiling point perfluoropolyether(PFPE) oil to provide thicker layers at lower cost. In some cases, aPFPE oil such as Fomblin YR 1800® sold by the Solvay Solexis Company maybe used. The boiling point of such a PFPE oil may be about 220 degreesC. to about 275 degrees C. for some embodiments.

Regarding the processing of some inner luminal layer embodiments 48, themanufacturer recommends in some cases that these amorphous fluoropolymercoatings be annealed above the boiling point of the solvent used andthen tempered for several minutes above the glass transitiontemperature, Tg, of the solid amorphous fluoropolymer film which may beabout 160 degrees C. for Teflon AF 1601® and about 240 degrees C. forTeflon AF 2400®. Exposure to these temperatures might be detrimental forthe PCTFE tube and other low melt plastics such as Pebax® used for theover-jacket 54 on the optional metal braid 52 of the multi-layercatheter tube 38 of the liquid core ablation catheter 22. In someembodiments, Pebax® materials may have a melting temperature of about135 degrees C., which is well below the recommended processingtemperatures to both remove the solvents and get the materials above theTg of the amorphous fluoropolymer. Method embodiments discussed hereinwere specifically developed to enable the application of these filmsonto an inner luminal surface of a PCTFE tube (or the like) to createthe inner luminal layer 48 of the ablation catheter 22. In some cases,these techniques use relatively lower process temperatures for longertime durations to achieve workable amorphous fluoropolymer inner luminallayers 48, as shown in FIG. 14, for multi-layer catheter tubes 22 whichmay then be filled with a liquid core 40 such as water or saline.

For some embodiments, a method of generating a multi-layer catheter tube38 may include a drip coating method whereby a solution of amorphousfluoropolymer or mixtures thereof are dissolved in solution such asFluorinert FC-40® from 3M at concentrations high enough to provide atleast a 5 micron or more layer thickness per coat. One or moremulti-layer catheter tubes 38 may be mounted vertically and cleaned onthe inside luminal surface with isopropyl alcohol or the like. The innerluminal surface of the catheter tube 38 may then be coated with thesolution of amorphous fluoropolymer for a given dwell time and annealedat temperatures less than about 100° C. or the melting point of themultilayer catheter material for times sufficient to remove all thesolvent. In some cases, dwell time at temperatures of less than about100° C. may be up to about 4 hours. The lower temperatures for annealingmay be configured or otherwise selected in order to prevent thermaldamage to the polymer materials of the multi-layer catheter tube 38 towhich the coating is being applied. This drip coating process may berepeated multiple times to produce an inner luminal layer 48 thicknessand uniformity that encapsulates or otherwise contains high power laserenergy at a wavelength of about 308 nm in the resulting waveguide coreof an ablation catheter 22 constructed from such a multi-layer cathetertube 38 and core-inner luminal layer junction therein. After processing,the multi-layer catheter tube 38 may be filled with an appropriate coreliquid 40 and sealed with suitable windows at both proximal and distalends thereof.

For some embodiments, the inner luminal layer 48 may also be thickenough to smooth out any surface irregularities on the inner surface ofa drip coated tube, such as a base layer tube 50 made from PCTFE, FEP orthe like. For some embodiments, a thickness of about 5 microns to about15 microns for the low IR internal material of the inner luminal layer48 might provide for an efficient coating. In some cases, Teflon® FEP orother fluoropolymer based materials may be used as an alternative toPTCFE for making base layer tubes 50 (see FIG. 14), however, there maybe issues with regard to keeping core fluids 40, such as water corefluids, from diffusing out of the liquid core ablation catheter 22during shelf life storage. Packaging the finished and sterilized liquidcore ablation catheter 22 in a high humidity package may mitigate thisproblem in some cases, particularly in instances where FEP is used.Suitable materials for such a package may include an openable enclosuremade from metal coated plastic, PCTFE or any other suitable materialcapable of producing a hermetic or hermetic type seal that is sealableabout a finished ablation catheter or catheter system and is suitablefor a desired type of sterilization such as gamma e-beam or the like.

Other methods for forming such a low index layer from these materialsmay include extruding a thin layer, for example, of solid Teflon AF2400® or Teflon AF 1601®, over a smooth polished metal mandrel to formthe inner luminal layer 48 of the multi-layer catheter tube 38 of theliquid core ablation catheter 22. In some cases, such an extruded thinlayer of low index material may have a thickness of about 5 microns toabout 50 microns. Once the amorphous fluoropolymer inner luminal layer48 is extruded over the mandrel, the outer surface 76 (shown in FIG. 14)of the inner luminal layer 48 may then be etched to promote surfaceadhesion thereto. A thicker wall PCTFE base layer tube 50, or base layertube 50 made from another suitable material, such as FEP, may then beover extruded onto the etched outer surface 76 of the inner luminallayer 48, followed by braiding of an optional multi-filament braid 52over the outer surface of the PCTFE tube 50. Then an over-jacket 54 maybe extruded over an outer surface of the braided layer 52 and PCTFE basetube 50. For some embodiments, the mandrel may then be removed from themulti-layer catheter tube embodiment 38. The tubular inner lumen 78 thatremains once the mandrel has been removed may then be filled withtransmissive liquid 40 and sealed with optical windows at each end,specifically an input optical window 80 at the proximal end 84 (shown inFIGS. 3 and 6) of the multi-layer catheter tube 38 and an output opticalwindow 82, as shown in FIG. 8, at the distal end 86 (shown in FIG. 3) ofthe multi-layer catheter tube 38. The optical windows 80 and 82 may alsobe transparent to the wavelength of laser energy to be guided therein.

Some methods may include placing multiple coating layers of an amorphousfluorocarbon material dissolved in a solvent over a mandrel wire withheat annealing between layers to above the Tg of the polymer to form theinner luminal layer 48. The outer surface 76 of the inner luminal layer48 may then be etched in order to facilitate adhesion thereto. A PCTFEbase layer tube 50, or base layer tube 50 made from another suitablematerial, may then be over-extruded or otherwise applied over the outersurface 76 of the inner luminal layer 48 with a subsequent optionalbraid 52 applied to an outer surface of the base layer tube 68 and overjacket 54 added to an outer layer of the braid 52 and base layer tube 50to complete the multi-layer catheter tube 38. In this example, all thehigh temperature annealing is done with a high temperature mandrel wirebefore the plastics are overlaid. No matter which method is used, thePCTFE base tube 68 is independent of the inner luminal layer 48 whichmay be a thin low IR coating where all the refraction of the guidedlaser energy takes place. In some cases, the thickness of this thininner luminal layer 48 must be at least several wavelengths thick forrefraction as discussed above.

This method may also include coating a mandrel wire with a concentratedsolution of an amorphous fluoropolymer dissolved in a solvent. Thepercentage of solids may be greater than 10% for maximizing wallthickness per coating layer. The coated mandrel wire may then beannealed above the boiling point of the solvent, which may be FC-40whose bp is 155° C. and then annealed up to 30 minutes at or above theglass transition temperature, Tg, of the solid fluoropolymer, which forTelflon AF 1601® may be about 160 degrees C. The thickness of this layermay be about 10 microns to about 50 microns for some embodiments. Thislayer may then etched and over extruded with a water barrier layer suchas PCTFE, braided and then overjacketed.

The input window 80 and output window 82 enclosing the fluid volume 40of the fluid core ablation catheter 22 generally include a material witha high transparency to the ultraviolet high power light pulses from theexcimer laser or other suitable high power laser sources. The inputoptical window 80 as shown in FIG. 6 extends past the interface with themulti-layer catheter tube 38 in order that input laser energy spill overfrom an associated optical coupler 20 does not impinge on themulti-layer catheter tube 38 which could be heated and damaged. Atubular capillary shield 88 (see FIG. 6) may also be placed over theelongated cylindrical window 80 to further shield the catheter tube 38.The input optical window 80 may have a numerical aperture (NA) that isless than or matches the NA of the core fluid 40 of the ablationcatheter 22 for optimum coupling in some cases. For some embodiments,the input optical window 80 may include a silica core silica cladwindow, but it may also include an optically polished silica rod that isradially surrounded by an air interface. The input optical window 80 ofthe ablation catheter 22 may also include a silica rod 90 (see FIG. 10)that has a low index amorphous fluoropolymer coating 91 such as TeflonAF 1601® or similar material applied to an outer surface thereof. Forsome embodiments, the input optical window 80 may have an outer diameteror transverse dimension of about 0.5 mm to about 1.5 mm, morespecifically, about 0.8 mm to about 1.2 mm. The input window 80,capillary shield 88 and proximal end of the ablation catheter 22 areheld in alignment and position for efficient coupling by a coupler body89, as shown in FIG. 6, which includes a barrel member made from a highstrength material with an inner lumen disposed therein. The proximal endof the ablation catheter 22 and distal end of the window 80 abut eachother within the lumen of the barrel of the coupler body 89 as shown inFIG. 7. The capillary shield 88 may extend over the operative junctionbetween the proximal end of the catheter tube 38 and distal end of theinput window 80.

The output optical window 82 as shown in FIG. 10 may have an overalllength selected to minimize stiffness of the distal end 34 of theablation catheter 22. In some cases, the output optical window 82 mayhave a length less than about 10 mm, more specifically, less than about8 mm, even more specifically, less than about 6 mm, to allow the tip tonegotiate curves in the body lumen. This output optical window 82 mayhave a numerical aperture equal to or greater than the numericalaperture of a tubular body portion of the liquid core ablation catheter22 for maximum coupling of laser energy out of the liquid core 40. Thisoutput optical window 82 again may include a high NA optical fiber or asilica rod 90 coated with a low index amorphous fluoropolymer coating91. For some embodiments, the output optical window 82 may have an outerdiameter or transverse dimension of about 0.5 mm to about 1.5 mm, morespecifically, about 0.8 mm to about 1.2 mm.

In order to protect the output optical window 82 from stresses and toease passage of the fluid filled ablation catheter 22, a tapered metalhousing 96 may be used to encapsulate the output optical window 82 asshown in the embodiment of FIG. 10. The output window 82 assembly at thedistal end 34 of the ablation catheter 22 may be arranged with theproximal end 100 of the output optical window 82 extending proximallybeyond a proximal end 98 of the tapered metal housing 96. The proximalend 100 of the output optical window 82 may extend proximally slightlyinto the core liquid 40 of the ablation catheter 22 in some cases asshown in FIG. 10. The tapered metal housing 96 may include an inner borethat extends the length of the tapered metal housing 96 from a proximalend to a distal end thereof. An inside surface 104 of the inner bore maybe sized to fit closely with an outer surface 102 of the coating 91 ofthe output optical window 82 in some cases such that the output opticalwindow 82 is stabilized laterally relative to the tapered housing butwith enough gap to allow materials such as adhesives to extend therein.In some instances, the tapered metal housing 96 may be secured to theoutput optical window 82 by any suitable means such as by crimping,adhesive bonding, brazing, soldering or the like. In some cases, thetapered metal housing 96 may be so secured such that there may be littleto no gap between the inside surface 104 of the inner bore of thetapered metal housing 96 and the outer surface 102 of the coating 91output optical window 82. The tapered metal housing 96 may include atapered distal section 110 that tapers down in outer diameter ordimension from a nominal outer diameter. The tapered distal section 110may taper down to a reduced diameter or transverse dimension that may beup to about 0.012 inches larger than an outer transverse dimension ordiameter of the output optical window 82. In some cases, the tapereddistal section 110 may have a wall thickness at the distal end of thetapered distal section 110 of about 0.003 inches to about 0.005 inches.The tapered metal housing 96 may also include a stepped portion 111 thatextends proximally from a proximal shoulder surface 112 of the tapereddistal section 110. The stepped portion 111 may have a thin walldisposed between the inner bore and an outer surface 108 that has anouter transverse dimension or diameter that is small enough to be pushedinto the inner lumen of the multi-layer catheter tube 38. In some cases,the wall thickness of the stepped portion 111 may be about 0.002 inchesto about 0.006 inches, more specifically, about 0.003 inches to about0.004 inches.

An outer surface 102 of the coating 91 of the output optical window 82may be bonded to the inside surface 104 of the metal housing 96 with anysuitable adhesive 106, such as a medical grade class VI adhesive. Theinside surface 104 of the metal housing 96 may also be secured to theouter surface 102 of the output optical window 82 by any suitable methodincluding crimping, adhesive bonding, soldering, brazing or the likedepending on whether the window 82 is an all glass embodiment or polymercoated embodiment. The outer surface 108 of the stepped portion of themetal housing 96 may be secured to a surface such as an inner luminalsurface 66 of the catheter tube 38 by bonding, such as adhesive bonding,or any other suitable method. The tapered distal section 110 of themetal housing 96 may provide for a more efficient cutting tip during thelaser ablation process in that the configuration may provide for moreactive cutting area relative to the non-cutting area at the distal endof the ablation catheter embodiment 22. In addition, the tapered end 110of the metal housing 96 may facilitate passage of the ablation catheter22 through a lumen created by the laser ablation process. For someembodiments, an outer surface of the tapered end or section 110 may forman angle with respect to a longitudinal axis 109 of the ablationcatheter 22 indicated by arrow 113. The angle 113 of the tapered end 110of the metal housing 96 may be up to about 5 degrees in some cases, morespecifically, about 1 degree to about 2 degrees, for some embodiments.In other embodiments, the angle 113 may be up to about 8 degrees, morespecifically, about 6 degrees to about 8 degrees. Further, the metalhousing 96 may provide mechanical support and strength to the outputoptical window 82 which may be made from brittle or relatively fragilematerials, such as quartz, silica or the like. The tapered metal housing96 may be made from a single piece of high strength metal such asstainless steel, NiTi, titanium or the like. Depending on the metalmaterial of the tapered metal housing 96, the tapered metal housing 96may be visible under fluoroscopic imaging and may be configured to serveas a radiopaque marker for the distal end of the liquid core ablationcatheter 22. Other metals such as gold, tantalum, platinum or the likemay also be included in the tapered metal housing 96 in order tofacilitate radiopacity of the tapered metal housing 96.

Specific examples for use of the liquid core ablation catheter 22 arediscussed herein that are directed to clearing obstructions inperipheral arteries of a patient, but similar approaches may be used forcoronary arteries and other lumens 118 in the human body. Additionally,the unique problems of stenosed AV fistulas can be addressed withsimilar catheters that use liquid filled UV ablation catheter designswith various guidance methods. To initiate a percutaneous procedure, ashort introducer sheath 323 may be placed into an artery of the groin ofa patient or a fistula vein (as shown in FIG. 58). All other devices maygenerally be introduced through this introducing catheter, which mayinclude a hemostatic valve to eliminate blood flow out of theintroducing catheter during the procedure. Contrast fluid may beintroduced through this introducer sheath or a longer introducingcatheter may be inserted through the sheath over a guide wire 56, asshown in FIG. 31, to locate this catheter near a target lesion 116disposed within the patient's anatomy.

In some cases, a method embodiment for using a liquid core ablationcatheter system 22 may include placing the low profile support catheter26 through the introducing sheath and advancing the support catheter 26distally into close proximity to a target lesion or material 116 asshown in FIG. 28. In some instances, the support catheter 26 may beadvanced, guided or positioned over a guidewire 56 during this process.If a guiding device such as a guidewire 56 is used for advancing thesupport catheter 26, the guidewire 56 may then be removed once thedistal end 120 of the support catheter 26 is disposed adjacent a targetsite or lesion 116. Once the guidewire 56 is removed from the innerlumen 28 of the support catheter 26, the liquid core ablation catheter22 advanced distally within the inner lumen 28 of the support catheter26 to the target lesion 116 as shown in FIG. 28. Saline may then beflushed through the inner lumen 28 of the support catheter 26 and aroundan outer surface of the liquid core ablation catheter 22 to remove bloodfrom the tip of the ablation catheter 22. The laser source 10 may thenbe energized by depressing the footswitch 16 and laser energy at a levelsufficient to ablate tissue then be emitted from the distal end 34 ofthe ablation catheter 22.

Upon activation of the laser, the distal end of the ablation catheter 22may be advanced distally in an axial orientation into the target lesion116 by a distance of about 5 to 10 mm for some embodiments, while thesupport catheter 26 remains substantially stationary with regard to itsaxial position. The support catheter 26 may then be advanced distallyover the ablation catheter 22 and through the lumen 122 created by theactive ablation catheter 22 until the distal tip 120, as shown in FIG.4, of the support catheter 26 is substantially even with the distal tip34 of the ablation catheter 22 as shown in FIG. 29. The relativepositions of the respective distal ends 120 and 34 of the supportcatheter 26 and ablation catheter 22 may be determined by fluoroscopicimaging of the respective radiopaque marker bands 31 at the respectivedistal ends 120 and 34. The process is repeated as shown in FIG. 30until the ablation catheter 22 crosses the lesion 116 as shown in FIG.31. The ablation catheter 22 is removed with the support catheter 26left in place and a guidewire 56 is advanced though the newly createdchannel or lumen 122. The support catheter 26 may then be retracted asshown in FIG. 32. Other devices, such as a balloon or a stent, may thenbe deployed over this guidewire 56 to achieve the necessary openingdiameter in the vessel for adequate blood flow. If the laser catheter 22produces a sufficient lumen 122, then no further treatment withadditional devices is required in some instances.

For such a procedure, the support catheter 26 may be configured to havea low profile with thin walls to be able to follow the ablation catheter22 through the lesion 116 and maintain the ablation end parallel to thelumen 122 to prevent perforation. To achieve this, the support catheter26 may be a multilayer design with a thin wall liner 124 of a lowfriction Teflon®, such as polytetrafluoroethylene (PTFE) to allowpassage of the ablation catheter with ease. An embodiment of thestructure of a suitable support catheter is shown in FIG. 18.

Referring to FIG. 18, this liner 124 of the support catheter 26 may havean over layer or base layer tube 126 then a metal braid layer 128disposed or braided over the base layer tube 126 to achieve pushabilityand kink resistance and torque. The base layer disposed over the PTFEliner 124 may have a high durometer with a very thin coating and anideal material may include a polyimide base layer tube 126 covered witha thin over-jacket 130 of a lower durometer material for flexibilityover the braid material layer 128. A wall thickness of the supportcatheter 26 of less than about 0.005″ may be used for low profile forpassage of the support catheter 26 through the opening or lumen 122 madeby the liquid core ablation catheter 22. In essence this method mayproduce a result which is equivalent to a result achieved by using anexternal guidewire 56 for location of a cutting tip of an over-the-wiretype design of the ablation catheter 22 as shown in FIGS. 15 and 16. Theinner lumen 28 of the support catheter 26 may also include sufficientspace or cross sectional area to accommodate both the ablation catheter22 and a lumen or longitudinal space therebetween for flow of saline. Aflow of saline or other desired fluid between an outside surface of theliquid core ablation catheter 22 and an inside surface of the innerlumen 28 of the support catheter 26 may be used to clear the blood whichis disposed at the target lesion 116 site. In some cases, the saline maybe introduced into the inner lumen 28 of the support catheter 26 with asyringe 19, as shown in FIG. 1, coupled to the Y connector 32 of thecatheter system 27 as shown in FIGS. 1 and 2.

Some support catheter embodiments 26 may be straight as shown in FIG. 19or have an angled tip as shown in the support catheter embodiment ofFIG. 21 depending on the vessel contour at the lesion site. The supportcatheter 26 may have a low friction lubricious outer coating 132 on anouter surface 134 thereof (as shown in FIG. 18) for low friction passagethough tissue follow the ablation catheter 22 through the lumen 122created by the ablation catheter 22 through the target lesion 116.Visualization of the location of both the support catheter 26 and theablation catheter 22 in the vessel lumen 118 and with respect to eachother may be made by means of one or more radiopaque markers 31 or 136disposed on the respective catheters at desired locations and with aleast one marker located at each distal tip (120 and 34 respectively) ofthe catheters.

Interventional physicians often rely on a guidewire 56 for advancingmultiple devices to treat a lesion 116 within a patient's vasculatureand to maintain the position of a catheter inside the lumen walls. Somemethod embodiments discussed herein may include the use of a guidewire56 to advance and/or position the support catheter 26. Once the supportcatheter 26 is properly positioned at a desired site within thepatient's body, the guidewire 56 may then be removed and replaced withan ablation catheter such as the liquid core ablation catheter 22. Someinterventionalist's may prefer the protection of a guidewire 56 to placeother devices over in case of adverse event. In such cases, the ablationcatheter 22 may be removed and a guidewire 56 inserted through the innerlumen 28 of the support catheter 26 and other treatment devices may thenbe passed over the guidewire 56 through the inner lumen 28 of thesupport catheter 26. In addition, the support catheter 26 may be removedbefore inserting other devices in some cases. One or more separateguidewire lumens 60 and 62 may also be attached to or integral with thesupport catheter 26 as shown on the support catheter embodiment 26′″ ofFIGS. 26 and 27. Additionally, a guidewire lumen may be added to theablation catheter 22′ as shown in FIGS. 15 and 16.

In some cases, a separate guidewire lumen 60 or any of the guidewirelumens discussed herein may be suitable for passage of a 0.014″ sizedguidewire or the like may be used for additional protection. In somecases, this guidewire lumen would only have a short length at the distalend for a rapid exchange type configuration. This configuration couldapply to the both the ablation catheter 22′ and the support catheter26′″. That way the physician would always have a guidewire present incase of an adverse event and has the ability to withdraw the liquid coreablation catheter 22 and advance a guidewire 56 over a total occlusionafter the dense cap entrance to the total occlusion is cleared by energyemitted from the liquid core laser ablation catheter 22 as shown in FIG.32. For some embodiments, the guidewire lumens 60 and 62 may have alength of at least about 10 cm. In addition, the respective distal portsof the guidewire lumens 60 and 62, which may be disposed along an outersurface of support catheter embodiments 26′″, may be disposed proximallyfrom a distal end of the support catheter 26′″ by at least about 5 mm.

For some embodiments, a support catheter such as the support catheter26′″ may have multiple guidewire lumens 60 and 62 as shown in theembodiment of FIGS. 26 and 27, a support catheter such as the supportcatheter 26″ may have a tapered distal section as shown in theembodiment of FIG. 20, and the support catheter 26′ may have a bend atthe end as shown in the support catheter embodiment of FIG. 21 tonegotiate bends in the artery or to displace the ablation catheter 22towards an eccentric plaque. The multiple guidewire lumens 60 and 62 maybe used for saline flush, contrast injection or for passage of aguidewire 56 in some cases.

For some indications, it may be desirable to make a channel in apatient's vessel lumen that is larger in transverse dimension than atransverse dimension of the ablation catheter 22 itself. For some suchcases, after the liquid core ablation catheter 22, or any other suitableablation catheter embodiment discussed herein, forms an initial channeland opens an occlusion 116 in a patient's vessel 118, a guidewire 56 orother device may then be inserted in the opening or newly formed channel122. The ablation catheter 22 may then be activated to emit ablationenergy and advanced through the initial channel 122 adjacent thesubstantially parallel guidewire 56 to produce a lumen 122′ which islarger than the lumen made with the first active pass of the ablationcatheter 22. Such a technique embodiment is shown in FIGS. 33-35.Embodiments of this procedure may be completed with a second guidewire56′ in a second guidewire lumen 60 or 62 of a support catheterembodiment 26′″ and a final pass made. This method may produce a lumen122′ having a larger inner transverse dimension or diameter andcorresponding larger transverse cross section than an outer transversedimension or diameter or cross section of the ablation catheter 22 usedto make the initial channel 122. During this type of method embodiment,the guidewire placements after the first or initial lumen is made blockpart of the initially created lumen which laterally forces the distalend of the liquid core ablation catheter 22 up against the remainingplaque 116. Such partial filling the first or initial channel with one,two, three or more guidewires 56 and 56′ forces the ablation catheter 22to ablate tissue disposed laterally with respect to the initial channel122 formed by the ablation catheter 22. Without the guidewire placementin the initial channel 122, the ablation catheter 22 would likely justgo through the first or initial lumen 122 on a second pass with nofurther ablation or channel widening or increase in cross sectionalarea. Such an increase in cross sectional area of the ablation channelallows more blood or other fluid to flow therethrough for a fixedpressure.

Referring to FIGS. 37-42, a variety of manufacturing steps are shownwhich may be useful for some or all of the processing method embodimentsdiscussed above. In particular, FIG. 37 illustrates a polished metalmandrel 140 being passed through an extruder device 142 and applying alayer of amorphous fluoropolymer 144 to an outer surface of the mandrel140. FIG. 38 shows a mandrel 140 having a solution of amorphousfluoropolymer 145 being applied to an outside surface of the mandrel 140by a spray coating device 146 to produce a thin layer of amorphousfluoropolymer 144. FIG. 39 depicts a mandrel 140 with a coating ofamorphous fluoropolymer solution 145 disposed in an oven 148 for thermalprocessing to drive off the solvent of the fluoropolymer solution 145.FIG. 40 shows a mandrel 140 with a layer of amorphous fluoropolymer 144applied thereto being passed through an extruder 142 to apply a layer ofbase tube material 150. FIG. 41 shows the mandrel 140 of FIG. 40 with alayer of amorphous fluoropolymer 144 and subsequent base layer tubematerial 150 being passed through a braiding device 152 to apply abraided layer 154 to the base tube layer 150. FIG. 42 shows the mandrel140 and layers 144, 150 and 154 being passed through an extruder 142 toapply an outer jacket layer 156. FIG. 43 shows an amorphousfluoropolymer solution 145 being injected into a catheter tube 38 by apressurized amorphous solution source 158 which may be further processedto remove the solvent from the solution 145 in an oven 148 as shown inFIG. 39.

FIG. 44 shows a distal portion of an embodiment of a liquid coreablation catheter that may have some or all of the properties of liquidcore ablation catheter 22 discussed above. Once again, in order toprotect the output optical window 82 from stresses and to ease passageof the fluid filled ablation catheter 22 through tissue during ablation,a tapered metal housing 196 may be used to encapsulate the outputoptical window 82 as shown in the embodiment of FIG. 44. The outputwindow 82 assembly at the distal end 34 of the ablation catheter 22 maybe arranged with the proximal end 100 of the output optical window 82extending proximally beyond a proximal end 198 of the tapered metalhousing 196.

The proximal end 100 of the output optical window 82 may extendproximally slightly into the core liquid 40 of the ablation catheter 22in some cases as shown in FIG. 44. The tapered metal housing 196 mayinclude an inner bore 197 that extends the length of the tapered metalhousing 196 in a proximal direction from a distal end 199 of the housing196 to a distal end 200 of a stepped portion 202 of the housing 196. Aninside surface 204 of the inner bore may be sized to fit closely with anouter surface 102 of the coating 91 of the output optical window 82 insome cases such that the output optical window 82 is stabilizedlaterally relative to the tapered housing but with enough gap to allowmaterials such as adhesives to extend therein. In some instances, thetapered metal housing 196 may be secured to the output optical window 82by methods such as by crimping, adhesive bonding, soldering, brazing orthe like. In some cases the tapered metal housing 196 may be securedsuch that there may be little to no gap between the inside surface 204of the bore 197 of the tapered metal housing 196 and the outer surface102 of the coating 91 of the output optical window 82. The tapered metalhousing 196 may include a tapered distal section 110 that tapers down inouter diameter or dimension from a nominal outer diameter. The tapereddistal section 110 may taper down to a reduced diameter or transversedimension that may be up to about 0.012 inches larger than an outertransverse dimension or diameter of the output optical window 82, insome cases up to about 0.010 inches larger. In some cases, the tapereddistal section 110 may have a wall thickness at the distal end 199 ofthe tapered distal section 110 of about 0.003 inches to about 0.005inches. The stepped portion 202 of the housing 196 may have a thin walldisposed over a reduced diameter portion 206 of a distal section of themultilayer catheter tube 38.

In some cases, the stepped portion 202 of the tapered metal housing 196may have the same or similar longitudinal length as that of the reduceddiameter portion 206 of the distal section of the multilayer cathetertube 38. In some cases, the wall thickness of the stepped portion 202may be about 0.002 inches to about 0.005 inches, more specifically,about 0.003 inches to about 0.004 inches. In some cases, the wallthickness of the reduced diameter portion 206 of the multilayer cathetertube 38 may be sized to have an overall outer diameter to substantiallymatch an inside diameter or transverse dimension of the stepped portion202 of the tapered metal housing 196. In addition, the inside surface ofthe stepped portion 202 may be secured to an outer surface of thereduced diameter portion 206 with an adhesive bond, crimp connection orthe like. In some instances, it may be desirable for an outside diameteror transverse dimension of the tapered metal housing 196 to be the sameas or substantially the same as an outside diameter or transversedimension of the nominal multilumen catheter tube 38 so as to provide asmooth regular transition between an outside surface of the taperedmetal housing 196 and an outside surface of the multilumen cathetertubing 38.

The outer surface 102 of the output optical window 82 may be bonded toan inside surface 204 of the metal housing 196 with any suitableadhesive 106, such as a medical grade class VI adhesive or the like. Forall glass embodiments of the output optical window 82, methods such assoldering or bronzing may be used. The inside surface 204 of the bore197 of the metal housing 196 may also be mechanically secured to theouter surface 102 of the output optical window 82 by methods such ascrimping or any other suitable mechanical method as discussed herein. Asdiscussed above, the tapered distal section 110 of the metal housing 196may provide for a more efficient cutting tip during the laser ablationprocess in that the configuration may provide for more active cuttingarea relative to the non-cutting area at the distal end of the ablationcatheter embodiment 22. In addition, the tapered end 110 of the metalhousing 196 may facilitate passage of the ablation catheter 22 through alumen created by the laser ablation process. For some embodiments, thetapered end 110 of the tapered metal housing 196 may have the same orsimilar configuration as that of tapered metal housing 96 discussedabove and as shown in FIGS. 10-12. In particular, the tapered end 110may form an angle 113 with respect to a longitudinal axis 109 of theablation catheter 22 indicated by arrow 113 in FIG. 10 of up to about 5degrees in some cases, more specifically, about 1 degree to about 2degrees, for some embodiments. In some instances, the tapered end 110 ofthe tapered metal housing 96, or any other tapered metal housingembodiment discussed herein, may form an angle 113 of up to about 9degrees, more specifically, of about 6 degrees to about 8 degrees.Further, the metal housing 196 may provide mechanical support andstrength to the output optical window 82 which may be made from brittleor relatively fragile materials, such as quartz, silica or the like. Thetapered metal housing 196 may be made from a single piece of highstrength metal such as stainless steel, titanium or the like. Dependingon the metal material of the tapered metal housing 196, the taperedmetal housing 196 may be visible under fluoroscopic imaging and may beconfigured to serve as a radiopaque marker for the distal end of theliquid core ablation catheter 22. Other metals such as gold, tantalum,platinum or the like may also be included in the tapered metal housing196 in order to facilitate radiopacity of the tapered metal housing 196.

FIGS. 46-50 illustrate an embodiment of a high energy laser coupler 220that may be operatively coupled to a proximal end of any of the liquidcore ablation catheters embodiments 22 discussed herein as well as anyother suitable laser ablation catheter. For some embodiments, the highenergy laser coupler 220 may include a coupler body 222 that has aproximal section 224 with a cylindrical outer surface 226 and an innerbore 228 which is disposed concentrically within the cylindrical outersurface 226. The inner bore 228 extends distally from a proximal end 230of the coupler body 222 to a proximal end 232 of a window connector bore234. The window connector bore 234 is disposed at a distal end of theinner bore 228. The coupler body 222 also includes a distal section 236extending distally from the window connector bore 234.

A window connector body 240 includes a proximal section 241 with acylindrical outer surface which may be configured to fit closely withinan inside surface of the window connector bore 234 of the coupler body222. A flange portion 244 of the window connector body 240 is disposedat a distal portion or distal end of the proximal section 241 andextends radially outward from a nominal outer surface 246 of theproximal section 241 of the window connector body 240. The windowconnector body 240 also includes a stepped portion 250 which extendsdistally from the proximal portion and has an outer diameter ortransverse dimension that is less than an outer diameter or transversedimension of the proximal section 241 of the window connector body 240.The outer diameter of the stepped portion 250 may be configured toextend within an inner lumen of a proximal section of the multilayercatheter tube 38. An outer surface 252 of the stepped portion 250 may besecured to an inside surface of the proximal section of the multilayercatheter tube 38 by an adhesive bond, crimp bond or the like. An innerbore 254 extends the length of the window connector body 240 from aproximal end 242 to a distal end 245 thereof. The inner bore 254 may bea straight bore that is configured to fit closely with an outer surface256 of an optical input window 80 disposed within and secured to theinner bore 254 of the window connector body 240. The outer surface 256of the optical input window 80 may be secured to an inside surface ofthe inner bore 254 of the window connector body 240 with an adhesivebond, crimp bond, solder bond, braze bond or the like. In some cases, itmay be desirable for the bond between the outer surface 256 of the inputoptical window 80 and the inside surface of the bore 254 of the windowconnector body 240 to be fluid tight.

In some instances, a proximal end of the optical input window 80 mayextend proximally from a proximal end 242 of the proximal section 241 ofthe window connector body 240. As shown in FIGS. 49 and 50, a proximalportion of the flexible waveguide catheter tube 38 is disposed over thestepped portion 250 of the window connector body 240 with a cylindricalmetal sleeve 260 disposed over the proximal portion of the flexiblewaveguide catheter tube 38. The cylindrical metal sleeve 260 may bedisposed so at to secure an inside surface of the catheter tube 38 to anoutside surface of the stepped portion 250 of the window connector body240 in a fluid tight seal. The inside surface of the multilayer cathetertube 38 may be secured to an outside surface of the stepped portion 250with an adhesive bond 263. In some cases, an inside surface 262 of themetal sleeve 260 may be secured to an outside surface of a proximalportion 267 of the multilayer catheter tube 38 with an adhesive bond263, with a crimp body or the like. In addition, a potting material 264such as an adhesive or the like may be used to provide mechanicalsupport and strain relief between an outer surface of the multilayercatheter tube 38 and an inside surface of a back bore 266 of the distalsection of the coupler body 222.

The optical input window 80 may include a length of multi-mode opticalfiber in some instances. In some embodiments, the optical input window80 may extend distally of a distal end 245 of the stepped portion of thewindow connector body 240 making direct contact with liquid core fluid40 of the liquid core ablation catheter. In some instances, the opticalinput window may have axial length of about 0.5 inches to about 1 inch.For some embodiments, the stepped portion of the window connector bodymay have a wall thickness of about 0.002 inches to about 0.004 inches.

Regarding packaging and transportation of liquid core ablation catheterembodiments discussed herein, certain conditions or structures may bedesirable in order to keep the catheter embodiments in good workingorder. In some cases, it may be important to maintain a minimum vaporpressure of liquid in the environment surrounding some liquid coreablation catheter embodiments 22 in order to prevent loss of core fluid40 during storage or transportation of the catheter 22 due to diffusionthrough the catheter tube 38 (see FIG. 7). It may also be important tominimize temperature extremes to which some liquid core ablationcatheter embodiments are exposed. FIG. 51 shows a liquid core ablationcatheter package assembly 250 that includes a thin walled hermeticallysealed enclosure 252 including an interior volume 254. In some cases, amaterial of the enclosure 252 may be suitable for gamma sterilization. Aliquid core ablation catheter 22 is shown disposed within the interiorvolume 254 of the hermetically sealed enclosure 252, however, anysuitable liquid core ablation catheter including any of the liquid coreablation catheters 22, 22′ or the like, discussed herein may be sopackaged. A second liquid 256 is disposed within the interior volume andis configured to maintain a vapor pressure within the interior volume254 sufficient to prevent loss of a liquid 40 of a liquid core 40 of theliquid core ablation catheter 22 due to diffusion of the liquid core 40into the interior volume 254. In some cases, it may be desirable to usea second liquid 256 which is soluble in or miscible with the liquid inthe core 40 of the ablation catheter 22. Thus the liquid core 40 of theliquid core ablation catheter 22 may include the same liquid as that ofthe second liquid 256 or the liquid core 40 and second liquid 256 may bedifferent liquids. The hermetic properties of the enclosure 252 preventsthe second liquid 256 from escaping the enclosure 252, thus only a smallamount of the second liquid 256 may be necessary. In some instances, thethin walled hermetically sealed enclosure 252 may be made from a thinmetalized plastic or a non-metalized thin plastic such as PCTFE thatfunctions as a suitable liquid vapor barrier in order to prevent escapeof the second liquid 256 from the interior volume 254 of the enclosure252. The thin walled plastic of the enclosure 252 may include heatsealed edges 253 in order to form the enclosure 252 from two flat thinsheets of the plastic material. The package assembly 250 may alsoinclude a liquid depot 258 that contains the second liquid 256 disposedwithin the interior volume 254. In some cases, the liquid depot 258 mayinclude a sponge or the like that may also be configured to absorb aliquid such as the core liquid 40 and be suitable for gammasterilization. In addition, the sealed enclosure 252 may be disposedwithin a substantially rigid box 260.

For some packaging methods and embodiments, the liquid core catheterembodiments 22, 22′ and the like, discussed herein may be placed in aspiral tube 270 filled with a second liquid 256 and sealed at both endsof the spiral tube 270 as shown in FIGS. 52-54. In some cases, thespiral tube 270 may be releasably secured to cardboard type supportsheet 271 with tabs 273 to hold the spiral tube 270 in the spiralconfiguration. This spiral tube container 270 is then sealed in aninterior volume 272 of a hermetically sealed pouch 274. The hermeticallysealed pouch 274 may include a hermetic metallized mylar heat sealedpouch 274, PCTFE pouch or other hermetic material. In some cases, thehermetically sealed pouch may be heat sealed along an entire edge at aseal line 275 as shown in FIG. 53. The hermetically sealed pouch 274 maythen be placed in a rigid box 276 for sterilization and shipping.Examples of such embodiments are shown in FIGS. 52-54. In addition,multiples of the boxes 276 may be transported in insulated boxcontainers i.e. Styrofoam lined boxes (not shown), to protect thecatheters from temperature extremes during shipping.

Some particular package assembly embodiments to extend a shelf life of aliquid core catheter may include a liquid core catheter 22 comprising acore liquid 40, a polymer spiral tube 270 which includes an inner lumen278 filled with a second liquid 256 that is soluble in or miscible withthe core liquid 40 of the liquid core catheter 22 and which is sealed atboth ends to contain the second liquid 256 in the inner lumen 278 of thepolymer spiral tube 270, and a sealed pouch 274 which is made of eithermetallized plastic or polychlorotrifluoroethylene that acts as ahermetic seal for liquids disposed within the sealed pouch. The sealedpouch 274 may also include a hermetically sealed inner volume or lumen272 with the polymer spiral tube and liquid core catheter 22 beingdisposed within the hermetically sealed inner volume 272.

In some cases, the spiral tube container 270 may include a firststraight section 282 that extends away from a spiral portion of thepolymer spiral tube 270. Such a straight section 282 may be useful formaintaining the straightness of an ablation catheter 22 disposed withinthe inner lumen 278 of the polymer spiral tube 270 for extended periodsof time. In some cases, the straight section 282 may have a length thatis about 10 cm to about 30 cm. A second straight section 284 may extendfrom the polymer spiral tube 270 at an end of the polymer spiral tube270 that is opposite that of the first straight section 282. The secondstraight section 284 may also have a length of about 10 cm to about 30cm for some embodiments. The second straight section 284 also includes aflared portion 286 at an end of the polymer spiral tube 270. The flaredportion 286 has a flared internal lumen profile configured to provide afluid tight seal 285 with an outside surface of a tapered strain relief287 of the laser coupler 24′ disposed within the inner lumen of theflared portion 286. The angle of the flared portion 286 maybe selectedsuch that the outside surface of the tapered strain relief 287 seats ina sealed relation to the inside surface of the flared portion 286 whenpushed into the flared portion 286. The laser connector 24′ and taperedstrain relief 287 may also be so seated such that it remains in fixedrelation relative to the flared portion 286 during storage due to thestatic friction between the inside surface of the flared portion 286 andthe outer surface of the strain relief 287 of the laser connector 24′.The sealed seating may also be facilitated by the elasticity of thematerial of the polymer spiral tube 270 at the flared portion 286. Auser may unseat the laser connector 24′ by merely pulling the laserconnector 24′ out of the flared portion 286. The end of the spiral tube270 opposite that of the flared portion 286 is sealed with a cap 290that is secured in fixed and sealed relation with the spiral tube 270.The spiral tube 270 may also be sealed at this location by any othersuitable method such as adhesive bonding, heat sealing or the like.

Another way to reduce or prevent diffusion loss of core fluid 40 from alaser ablation catheter during storage is to select one or morematerials for the multi-layer catheter tube 38 that are impervious todiffusion of the core liquid 40. As discussed above, some embodiments ofa liquid core ablation catheter 22 may comprise a multi-layer cathetertube 38 including a fluoropolymer material and an internal coating 48disposed on an inner surface of the catheter tube 38. In some cases, theinternal coating 48 may include an amorphous fluoropolymer having a lowindex of refraction of less than about 1.34. The liquid core ablationcatheter 22 may also have an outer layer 54 disposed on an outer surface68 of the multi-layer catheter tube 38, the outer layer 54 includingPCTFE material that acts as a barrier to liquid diffusion out of aninner lumen 46 of the catheter tube (see FIGS. 13 and 14). The baselayer tube 50 may also include PCTFE material or the like which isimpervious to diffusion of the core fluid 40. Such prevention of liquiddiffusion may include prevention of water vapor diffusion. The liquidcore ablation catheter 22 may also include a first solid window 80 thatseals the inner lumen 46 at a first end of the catheter tube 38 and asecond solid window 82 that seals the inner lumen 46 at a second end ofthe catheter tube 38 (see FIGS. 3 and 6).

The systems and methods discussed above may be used to treat a widevariety of occlusive conditions in patient vessels including some thatare difficult to treat by existing methods. A particularly difficultindication relates to vascular access required for dialysis procedures.Kidney dialysis is performed by accessing a patient's vasculature inorder to provide circulation of the patient's blood to a dialyzermachine. Typically, access to the patient's vasculature for dialysis isachieved by placing a pair of dialysis needles into an AV fistula 300 ofthe patient or a suitable vessel adjacent an AV fistula as shown inFIGS. 55 and 55A. The AV fistula 300 may be created in the patient'sbody with a surgical procedure by forming an AV fistula graft (AVG) 302as shown in FIG. 55 or by directly coupling a patient's artery 304 to apatient's vein 306 as shown in FIG. 55A. An AV fistula 300 may be usefulbecause it causes the vein 306 to grow larger and stronger in thevicinity of the AV fistula 300 for easy access to the vascular system308 of the patient. The AV fistula 300 is generally considered to be thebest long-term vascular access modality for hemodialysis proceduresbecause high pressure blood 310 in the vein 304 from the coupled arteryprovides adequate blood flow for dialysis and the AV fistula 300generally remains useful for 1-2 years and has a lower complication ratethan other types of dialysis access. If an AV fistula 300 cannot becreated in a patient or a patient's AV fistula access site becomesunusable due to a blockage or some other reason, a venous catheter maybe needed for dialysis access and such venous catheter access may have ahigh complication rate. It is estimated that over 300,000 patients aretreated each year in the USA for these types of procedures, and with anaging population, a 9% growth rate per year, is expected in patientsrequiring this procedure.

As discussed above, vascular access for dialysis may include a point forfluid communication into the bloodstream of a patient, such as adialysis patient, so that the patient can be properly connected to thedialysis machine. Without this vascular access point, repeated dialysiswould not be possible without the troublesome use of venous catheters orthe like. Generally speaking, an AV fistula 300 may be createdinternally and used for prolonged period of time. The most direct AVfistula creation involves a surgical procedure to put a lumen 312 of anartery 304 into direct fluid communication with a lumen 314 of a vein306, and allowing arterial blood, as indicated by arrows 316, to flowdirectly into the vein 306 as shown in FIG. 55A. The blood vessels ofthe arm are usually chosen e.g. at the wrist/forearm 318 or in the upperarm 319 of a patient. Due to the arterial pressure, the vein 306 whichmakes up an AV fistula graft or is disposed downstream of an AV fistulatypically increases in size and the walls of the vein would also thickenover time (not shown). Generally, it takes about 4 to 8 weeks for the AVfistula vein to mature and strengthen to a useable level suitable fordialysis access by needles. A pair of needles may then be inserted intothis enlarged and strengthened vein 306 to allow blood flow through thevein 306, indicated by arrows 317, to flow through the dialyzer using ablood pump on the dialyzer machine. For some treatment embodiments, itmay be desirable for a transverse dimension or diameter of the enlargedand strengthened AV fistula vein to expand to about 10 mm.

In addition to the creation of an AV fistula 300 by means of directlyconnecting an artery 304 to a vein 306, an AVG 302 may be created, asdiscussed above, which is an artificial blood vessel used to join aninner lumen 312 of an artery 304 into fluid communication with an innerlumen 314 of a vein 306 as shown in FIG. 55. Such an AVG 302 may be usedin some cases when the patient's own blood vessels are too small fordirect AV fistula construction. The AVG 302, which may be eitherstraight or looped, is typically disposed close to the surface of theskin of the patient for ease of needle access for dialysis or the like.The AVG 302 may be formed from an artificial material such as PTFE orthe like, or the AVG 302 may be an autologous graft obtained from thepatient's own body e.g. a sacrificial vein taken from the patient'sthigh or any other suitable location. AVGs 302 are most commonly placedin the upper arm 319, lower arm 318 or thigh. Two to four weeks aretypically allowed to pass before the AVG 302 is suitable for vascularaccess use. The two to four week delay may allow adequate timepost-operative for healing and sufficient growth of tissue to stabilizethe AVG.

Notwithstanding the common use of AV fistulas 300, vascular access stillrepresents the Achilles heel in today's hemodialysis treatment. In somepatients the vessels are unsuitable for primary arteriovenous fistulacreation. Thrombosis is also a leading cause of AV fistula failure aswell as intimal thickening, leading to stenosis by means of cellularproliferation. Enhanced cellular proliferation in human stenotic tissuederived from AV fistulas 300 results in high proliferation ratesassociated with endothelial cell coverage of the lumen and low localflow velocities due to blockages 320 as shown in FIGS. 56 and 57. Inparticular, problems with blockages 320 in AV fistulas 300 typicallyoccur at the junction of the vein 306 with the artery 304. The incidenceof stenosis in the first postoperative year may be 50% to 60% inhemodialysis AV fistulas 300 when constructed with the use of AVGs 302.AVG failure usually occurs within 18 months from creation of theassociated AV fistula 300. One problem with AV fistulas 300 is thecontinuing narrowing of the AV fistula 300 over time especially at thejuncture of the artery 304 with the vein 306. Vascular muscle cellsbegin growing inwardly causing thrombosis in the AV fistula 300 and/oradjacent vessels such as the vein 306. When this thrombus becomes large,blood flow 317 decreases and the AV fistula 300 ceases to be effective.

Non-surgical options for treating this narrowing condition of AVfistulas 300 is primarily balloon angioplasty type procedures which justremolds the hyperplasia but does not remove the material and therefore,may not improve the blood flow characteristics through the AV fistula300 over time. In particular percutaneous transluminal balloonangioplasty (PTA) of blockages 320 of AV fistulas 300 and adjacentvessels typically requires high pressure up to 30 atmospheres (atm)balloons to fully dilate the occluded vessel of the AVG 302 or adjacentvessel. Stenting, drug coated stents and photodynamic therapy have beenproposed to treat stenosed or otherwise blocked AV fistulas 300. Bloodthinning therapy may also used to minimize thrombosis in an AV fistula300, although none of these treatment methods are particularly effectivefor long term treatment. However, the type of blockage 320 present inthe AV fistula 300 and adjacent vessels appears to be similar to thetype of blockage seen in an in-stent restenosis (ISR) and therefore, acombination of laser ablation and drug eluting balloon (DEB) therapy maybe more effective for treatment yielding long term patency of a lumen ofan AV fistula 300 and/or vessels adjacent to the AV fistula 300.

Pulsed UV ablation at 308 nm is effective in ablating neointimalhyperplasia as well as thrombus. Pulsed UV laser energy may be used fortreating blockages 116 in coronary and peripheral arteries 119 for bothde nova and restenosed lesions as shown in FIGS. 28-36 and discussedabove. In addition, recent Food and Drug Administration (FDA) approvalhas been granted for the use of UV laser energy ablation of blockagematerial for treating in-stent restenosis (ISR). Recently publishedresults for ISR has shown that such blockages are different than de novaplaque in that such blockages are made up mostly of neointimalhyperplasia. The mechanism of ISR lesions appears to be due to smoothmuscle cell replication and accumulation of extracellular matrix. Theextracellular matrix is composed of various collagen subtypes andproteoglycans and over time constitutes the major component of themature restenotic plaque. Such extracellular matrix material does notappear to be susceptible to treatment by standard PTA, because thematerial of these type of restenosis lesions contains a large amount ofwater and the blockage material acts like a sponge which absorbs thewater giving a blockage material much of its volume. Compression of theblockage material from the force exerted by an expanded angioplastyballoon squeezes the water out of the blockage material but water isthen rapidly reabsorbed by the blockage material following a balloondilatation by PTA. The reabsorption of the water by the blockagematerial results in re-expansion of the blockage material into the lumenof the patient's vessel and thereby reoccludes the vessel. As such, thelong term results for treatment of ISR with PTA seems to be very poor.Furthermore, PTA with the use of drug-eluting balloons (DEB) coated forexample with paclitaxel-iopromide mixture has been shown to improve thelong term outcome in the treatment of de nova type lesions or blockages,but these methods have not fared as well when used to treat the plaqueformed by ISR. The best results for thus far for treating ISR have beenachieved with methods that include debulking of the blockage material ofthe ISR with laser ablation followed by DEB treatment.

To improve flow in AV fistulas, AVGs and vessels adjacent thereto whichhave narrowed or been occluded, in some cases, we propose using some orany of the embodiments discussed or incorporated herein of pulsed XeCl308 nm short pulsed excimer lasers coupled with a liquid core ablationcatheter having a solid output window (as discussed above) to ablate theblockage 320 which may include thrombosis and/or cellular plaque inorder to treat the point of vascular access provided by an AV fistula.See commonly owned U.S. patent publication no. 2013-0096545, filed Oct.12, 2012, which is incorporated by reference herein in its entirety.Optionally, the treatment of AV fistulas 300, AVGs, and adjacent vesselsby laser ablation may be combined with subsequent treatment with DEB.The liquid core ablation catheter 22 may also be configured to emit ared aiming beam from a distal end thereof to help visualize and guidethe distal end of the ablation catheter 22 inside the patient'svasculature 308. Pulsed excimer laser atherectomy at 308 nm may be usedto remove obstructions 320 in vessel lumens by photo dissociation, whichmay remove the material of the blockage 320 and produces patent circularlumens without thermal damage to the vessel wall.

For UV ablation of an AV fistula blockage 320, a shorter catheter can beused than that required to treat coronary vessels because the AV fistula300 is typically formed in the wrist region 318 or upper arm 319. Thus,the recanalization procedure for laser ablation may be performed usingvascular access directly into the vein 306 in the arm instead ofentering through the groin as for coronary and peripheral arterialatherectomy. Because there is not a need to go around tight curves, amultilayer catheter 22 or 22′ without a braided layer 52 (as shown inFIG. 13) can be used in most instances.

If the blockage 320 of a lumen of an AV fistula lesion is a totalocclusion, guidance for the laser ablation catheter 22 may be a supportcatheter 26, 26′ or 26″, with the support catheter being eitherstraight, tapered or angled at a distal section thereof as shown inFIGS. 20 and 21. In some cases, a deflectable tip support catheter 322(as shown in FIG. 62) may be used to position the distal tip 34 of theablation catheter 22 to a desired treatment site within a patient'svasculature 308. For non-total occlusions a UV liquid core ablationcatheter 22′ with a rapid exchange eccentric guide wire lumen 58 (seeFIGS. 16 and 26) that may be used to keep the ablation catheter 22′coaxial to a vessel being treated and also to guide the distal tip 34 ofthe laser ablation catheter 22′ within an AVG 302 from the artery 304 tothe vein 306. An introducer sheath 323 (see FIG. 58) may also beinserted into the patient's vasculature 308 with a distal end 324thereof disposed adjacent the occluded vessel followed by a guidingdevices such as a support catheter and/or guidewire 56 passed throughthe introducer sheath 323. The distal tip 324 of the laser ablationcatheter 22 is positioned to clear the blockage 320. In some cases, apatent AV fistula vein may have a diameter of about 10 mm, but theablation catheter 22 might only about 1.5 mm to about 2.1 mm for someembodiments.

In order to ablate a lumen having a transverse inner dimension which islarger than a transverse outer dimension of the ablation catheter 22, anangled tip 57 of a support catheter 26′ can be used to produce a largerlumen as shown in FIGS. 24, 25 and 33-36. A deflectable tip 324 of thedeflectable tip support catheter 322, as shown in FIG. 62, may be usedin a manner similar to the angled tip 57′ of support catheter 26′ shownin FIGS. 21 and 36. That is, the ablation catheter 22 may be axiallyadvanced through an inner lumen of the tubular deflectable tip catheter322 until the distal end 34 of the laser ablation catheter extendsslightly from a distal end of the deflectable tip catheter 322.Thereafter, the distal tip 324 of the deflectable tip catheter 322 maybe transversely deflected so as to transversely displace the distal tip34 of the ablation catheter prior and during axial advancement of thelaser catheter 22 and during ablation of the blockage 320. Thetransverse displacement of the distal tip 34 of the ablation catheter 22during axial advancement of subsequent ablation passes results in theablation of material of the blockage 320 that is transversely adjacentthe previous lumen made by previous ablation passes. The distal end 324of the deflectable tip catheter 322 can be either deflected, rotated orboth. A deflected deflectable tip 324 of deflectable tip catheter 322may be used to hold the distal end 34 of the laser ablation catheter 22in a transversely displaced position during axial advancement or toprovide nutation of the distal tip 34 as discussed with regard to FIGS.23-25 and 36.

The deflectable tip 324 may be deflected by a deflection angle,indicated by arrow 326, of up to at least about 45 degrees. Thedeflectable tip 324 may also have an axial length, indicated by arrow328, of about 2 mm to about 4 mm. Deflection of the deflectable distaltip 324 may be controlled by a knob 330 on a proximal handle portion 332of the deflectable tip catheter 322. Recent clinical studies, however,have shown that all the plaque of a blockage need not be removed whenfollowed by a DEB to achieve long term patency. Use of either aguidewire 56 or deflectable tip support catheter 322, or any othersuitable support catheter 26′, can position the laser catheter ablationtip 34 at the proper position for contact ablation of the blockage 320.Typically, PTA procedures for treating stenosed AV fistulas may use a 7French (2.3 mm diameter) support catheter.

Some embodiments of a method of treating an AV fistula 300 of a patientmay include inserting an introducer sheath 323 into a patient'svasculature 308 as shown in FIG. 58 to provide a conduit from a positionoutside the patient's body to a position within the patient's body. Aguiding device such as a guidewire 56 or support catheter 26′ or 322 maythen be advanced to the AV fistula and a liquid core ablation catheter22 or 22′ then advanced through an inner lumen of the introducer sheath323 and to a position adjacent a blockage 320. Such a blockage 320 maybe disposed within or adjacent the AV fistula 300. During advancement,the distal end 34 of the liquid core ablation catheter 22 or 22′ may beguided with the guiding device. In some cases, the guiding deviceincludes a guidewire 56 and guiding the distal end 34 of the liquid coreablation catheter 22′, as indicated by arrow 321, includes advancing theliquid core ablation catheter 22′ over the guidewire 56 as shown in FIG.59 with the guidewire 56 disposed within a guidewire lumen 58 as shownin FIG. 15. For some embodiments, the liquid core ablation catheter 22may include an eccentric guidewire lumen 58 with a distal end of theeccentric guidewire lumen 58 being disposed adjacent the distal end 34of the liquid core ablation catheter 22′. Such an eccentric guidewirelumen 58 may have an axial length of at least about 10 cm. For suchembodiments, axially advancing the liquid core ablation catheter 22′ mayfurther include axially advancing the liquid core ablation catheter 22′over the guidewire 56 disposed within such an eccentric guidewire lumen58.

In other embodiments, the guiding device may include a support catheter322 and guiding the distal end 34 of the liquid core ablation catheter22 comprises advancing a distal end 34 of the liquid core ablationcatheter 22 from a distal end 324 of the support catheter 322 as shownin FIG. 60. For method embodiments that include guiding with a supportcatheter 26′, 322 or the like, the distal tip 34 of the laser ablationcatheter 22 may be extended by a distance of up to about 5 mm from thedistal end 324 of the support catheter 322. For some method embodiments,the distal end 34 of the ablation catheter 22 may be advanced, asindicated by arrow 325 in FIG. 60, and guided by advancing a distal end324 of the liquid core ablation catheter 22 from a distal end 324 of thesupport catheter 322 up to about 5 mm from the distal end 324 of thesupport catheter 322 then axially advancing the support catheter 322relative to the liquid core ablation catheter 22 while holding theliquid core ablation catheter 22 stationary. The support catheter 322may be advanced until the distal end 324 of the support catheter 322 isdisposed substantially evenly with the distal end 34 of the laserablation catheter 22. The laser ablation catheter 22 may then beadvanced relative to the support catheter 322 for a distance up to about5 mm, and then this process repeated at least one additional time. Insome cases, this step and repeat process may be continued until theblockage of the AV fistula is completely traversed by the laser ablationcatheter 22. This step and repeat process may be the same as, or similarto the process shown in FIGS. 28-32 and discussed above.

For some method embodiments, a distal portion of the liquid coreablation catheter 22 may include a radiopaque marker 31 and a distal tip324 of the support catheter 322 may include a radiopaque marker 334. Forsuch an embodiment, guiding the distal end 34 of the liquid coreablation catheter 22 may be performed using the radiopaque markers 31and 334 under fluoroscopy to visualize and identify an axial position ofeach of the support catheter 322 and liquid core ablation catheter 22relative to each other while emitting pulsed ultraviolet laser ablationenergy from the distal end 34 of the liquid core ablation catheter 22.In certain instances, red light (not shown) may be emitted from a reddiode laser and from the distal surface 42 of the distal end 34 of theliquid core ablation catheter 22 and a position of the distal end 34 ofthe liquid core ablation catheter 22 visualized through skin of thepatient by visualizing the red light through the skin of the patient.

While being guided by a guidewire 56, support catheter 26′ or 322, orany other suitable guiding device, the liquid core ablation catheter 22or 22′ may be advanced through the blockage while emitting pulsedultraviolet laser ablation energy from a distal surface 42 or 340 (asshown in FIG. 17A) of the liquid core ablation catheter 22 or 22′thereby ablating the blockage 320 and debulking the blockage 320. Theliquid core ablation catheter 22 or 22′ may continue to be advanceduntil the blockage 320 is axially traversed by the distal end 34 of theliquid core ablation catheter 22 or 22′. Thereafter, the liquid coreablation catheter 22 or 22′ may be axially withdrawn or otherwiseremoved from the AV fistula vessel or vessels 302, 306, after theblockage 320 has been traversed. A neolumen 342 created by ablating anddebulking of the blockage 320 after removal of the liquid core ablationcatheter 22 or 22′ is shown in FIG. 63.

For some liquid core ablation catheter embodiments 22 or 22′ discussedherein, an active emitting surface of a distal end of the liquid coreablation catheter 22 or 22′ may include at least about 50 percent of atotal area of the distal end of the liquid core ablation catheter 22 or22′. FIG. 17A shows an end view of a liquid core ablation catheter 22′having an eccentric guidewire lumen 58 and a tapered distal end. Thesurface area of the active emitting surface 340 indicated by arrow 344is at least about 50 percent of the total area of the distal end surfaceof the liquid core ablation catheter 22′ as indicated by arrow 346. Theinactive dead space surrounding the active emitting area 340 is made upof the surface area of the distal end of the tapered metal tip 110. Itshould be noted that the active emitting surface 340 of the liquid coreablation catheter 22′ shown in FIG. 17A is a continuous, uninterruptedemitting surface within the diameter indicated by arrow 344. A similarratio of active emitting surface area 42 relative to total surface areaat the distal end of the liquid core ablation catheter 22 may also beused in some cases. This continuous, uninterrupted active emittingsurface is in contrast to other available ablation catheters that relyon a bundle of multiple fibers or waveguides. Due to the geometry ofbundling multiple fibers with round transverse cross sections, there isa predetermined limit on the packing efficiency due to the dead spacethat does not emit laser ablation energy disposed between adjacent fibertips. Liquid core ablation catheters 22 or 22′ that have a continuous,uninterrupted active emitting surface do not include this dead spacebetween bundled fibers and thus ablate tissue at the distal tip surfacefor contact ablation more efficiently.

Liquid core ablation catheter embodiments 22 or 22′ having a largepercentage of active emitting surface 42 or 340 relative to totalsurface area of the distal end produce more efficient ablation anddebulking of blockages being treated. For some embodiments, axiallyadvancing the liquid core ablation catheter 22 or 22′ may includeaxially advancing a liquid core ablation catheter 22 or 22′ that has amultilayer tube 38 with a base tube 50 made at least in part offluorinated material and an inner coating 48 disposed on an innersurface of the base tube 50 (see FIG. 15). Such an inner coating 48 mayinclude a material having a low index of refraction of up to about 1.34or less, and a biocompatible liquid core 40 which fills an inner lumen46 within the multilayer tube 38 and which is capable of transmittingpulsed 308 nm ultraviolet high energy pulsed radiation.

In some instances, during ablation and debulking of a blockage 320,pulsed ultraviolet laser ablation energy from a XeCl excimer laser 10 ata nominal output wavelength of about 308 nm and a repetition rate ofless than about 100 Hz may be directed into an input end of the liquidcore ablation catheter 22 or 22′. The pulsed ultraviolet laser ablationenergy is then transmitted through the ablation catheter 22 or 22′ andemitted from the active emitting surface 42 or 340 of the liquid coreablation catheter 22 or 22′. In some instances, emitting pulsedultraviolet laser ablation energy includes emitting pulsed ultravioletlaser ablation energy at a pulsed energy fluence greater than athreshold of ablation of a type of blockage material 320 being ablatedfrom a laser source 10 of the laser ablation energy comprising a XeClpulsed 308 nm excimer laser with a pulse duration of less than about 100nsec, and a repetition rate of less than about 100 Hz.

Once the blockage 320 has been completely traversed, the AV fistula andadjacent vessels, for example, AVG 302 or vein 306, may be furthertreated by treating the neolumen 342 created by the laser ablationprocess with a drug eluting balloon catheter 350 as shown in FIGS. 64and 65 in order to improve long term patency of the neolumen 342. Theneolumen 342 for purposes of this step may be any lumen previouslycrossed and treated by a UV ablation catheter including liquid coreablation catheters 22 or 22′ or any other such UV ablation catheterssuch as a fiber optic based ablation catheter. Such fiber optic basedablation catheters may also include multi-fiber fiber optic ablationcatheters (not shown). FIG. 64 shows a blockage 320 disposed within theAVG 302 being treated with a dilated DEB 350. An inflatable balloon 352of the DEB 350 is configured to expand within the blockage 320surrounding the balloon 352. As discussed above, when blockages 320 arebeing treated by PTA alone, it may be necessary to inflate the PTAballoon to high pressures such as up to about 30 atm. However, fortreatment embodiments that include laser ablation and debulking of ablockage 320 with subsequent treatment with DEB, the inflatable balloon352 of the DEB 350 may be fully effective when inflated to lowerpressures due to the effects of ablation and debulking of the materialof the blockage 320 prior to the DEB treatment. Such lower inflationpressures may have a benefit of generating less mechanical damage to awall of a vessel being treated which may also minimize injury responsemechanisms at the treatment site including subsequent hyperplasiaformation. In some cases, an inflatable balloon 352 of a DEB 350 may beinflated to a pressure of up to about 5 atm following ablation anddebulking of the same blockage 320.

The balloon 352 is also configured to elute materials such as drugs intotissue of the blockage 320 that surrounds the balloon 352 duringinflation as indicated by arrows 354 in FIG. 64. FIG. 65 shows ablockage 320 disposed within a vein 306 adjacent the AV fistula 300 andAVG 302 being treated with a dilated DEB 352. Once again the DEB 352 isshown eluting a drug into the tissue of the blockage 320 which surroundsthe DEB 352 as indicated by arrows 354 in FIG. 65. Advancement of theDEB catheter 350 in FIGS. 64 and 65 is carried out with the DEB catheter350 being advanced to the target treatment site over a guidewire 56. Asdiscussed above, the combination of treating soft spongy blockages withlaser ablation and debulking in combination with subsequent treatment byDEB 352 is believed to yield good long term patency results. In somecases, the DEB embodiment 352 may be configured to elute a suitable drugconfigured to control restenosis following an angioplasty procedure. Insome cases, treating the neolumen 342 of the blockage 320 with a drugconfigured to control restenosis following an angioplasty procedureincludes treating the blockage with a compound that includes paclitaxel.For some treatment embodiments, treating the blockage with a compoundincluding paclitaxel includes treating the blockage with apaclitaxel-iopromide mixture.

During advancement of the laser ablation catheter 22 and/or the supportcatheter 26′ or 322, a saline solution or contrast solution may beinjected through a lumen disposed between an outside surface of theliquid core ablation catheter 22 and an inside surface of the supportcatheter 26′ or 322 by a syringe 19 as shown in FIG. 58. The contrast orsaline solution may thus be emitted from the distal end of the supportcatheter 26′ or 322. In addition, if the support catheter 26′ or 32 isintroduced through an inner lumen of an introducer sheath 323, saline orcontrast solution may be injected through a lumen disposed between anoutside surface of the support catheter 26′ or 322 and an inside surfaceof the introducer sheath 323. For this configuration, the saline orcontrast solution will be ejected from the distal end of the introducersheath 323.

As discussed above, for some treatment methods, it may be desirable toform a neolumen 342 in a blockage 320 that has an inner transversedimension that is larger than an outer transverse dimension of theliquid core ablation catheter 22. For such method embodiments, thedistal end 34 of the liquid core ablation catheter 22 may be laterallyor transversely repositioned and then axially advanced through theblockage 320 for a second pass after a first ablation and debulking passwith the distal end 34 of the liquid core ablation catheter 22transversely re-positioned while emitting pulsed ultraviolet laserablation energy from the distal surface 42 of the liquid core ablationcatheter 22. Additional material of the blockage 320 may be therebyablated and debulked during the second pass with the distal tip 34 ofthe liquid core ablation catheter 22 so laterally repositioned. In orderto maintain the transverse repositioning of the distal end 34 of theliquid core ablation catheter 22 during the second ablation anddebulking pass, a support catheter 26′ having an angled distal sectionmay be used to transversely re-positioning the distal end of the supportcatheter 26′ while nutating the angled distal section of the supportcatheter during advancement and ablation. In some instances, a supportcatheter 32 having a deflectable distal section or tip 324 may be usedsuch as shown in FIG. 62. For such an embodiment, the distal end 34 ofthe liquid core ablation catheter 22 may be transversely re-positionedduring a second pass while ablating and debulking the blockage 320 whiletransversely deflecting the deflectable distal section 324 of thesupport catheter 322 and thus the distal end 34 of the liquid coreablation catheter 22 which extends slightly therefrom. For any of themethod embodiments discussed above, it may be desirable to deploy afilter device downstream (with regard to direction of blood flow) from ablockage 320 being treated in order to capture any thrombus or otherblockage material 320 which is removed from a blockage 320 but which isnot ablated.

With regard to the above detailed description, like reference numeralsused therein may refer to like elements that may have the same orsimilar dimensions, materials and configurations. While particular formsof embodiments have been illustrated and described, it will be apparentthat various modifications can be made without departing from the spiritand scope of the embodiments of the invention. Accordingly, it is notintended that the invention be limited by the forgoing detaileddescription.

The entirety of each patent, patent application, publication anddocument referenced herein is hereby incorporated by reference. Citationof the above patents, patent applications, publications and documents isnot an admission that any of the foregoing is pertinent prior art, nordoes it constitute any admission as to the contents or date of thesedocuments.

Modifications may be made to the foregoing embodiments without departingfrom the basic aspects of the technology. Although the technology mayhave been described in substantial detail with reference to one or morespecific embodiments, changes may be made to the embodimentsspecifically disclosed in this application, yet these modifications andimprovements are within the scope and spirit of the technology. Thetechnology illustratively described herein suitably may be practiced inthe absence of any element(s) not specifically disclosed herein. Thus,for example, in each instance herein any of the terms “comprising,”“consisting essentially of,” and “consisting of” may be replaced witheither of the other two terms. The terms and expressions which have beenemployed are used as terms of description and not of limitation, and useof such terms and expressions do not exclude any equivalents of thefeatures shown and described or portions thereof, and variousmodifications are possible within the scope of the technology claimed.The term “a” or “an” may refer to one of or a plurality of the elementsit modifies (e.g., “a reagent” can mean one or more reagents) unless itis contextually clear either one of the elements or more than one of theelements is described. Although the present technology has beenspecifically disclosed by representative embodiments and optionalfeatures, modification and variation of the concepts herein disclosedmay be made, and such modifications and variations may be consideredwithin the scope of this technology.

Certain embodiments of the technology are set forth in the claim(s) thatfollow(s).

What is claimed is:
 1. A package assembly to extend a shelf life of aliquid core catheter, comprising: a liquid core catheter comprising acore liquid; a polymer spiral tube which includes an inner lumen filledwith a storage liquid that is soluble in or miscible with the coreliquid of the liquid core catheter and which is sealed at both ends tocontain the storage liquid in the inner lumen of the polymer spiraltube; and a sealed pouch which is made of either metallized plastic orpolychlorotrifluoroethylene that acts as a hermetic seal for liquidsdisposed within the sealed pouch and which includes a hermeticallysealed inner volume with the polymer spiral tube and liquid corecatheter being disposed within the hermetically sealed inner volume. 2.The package of claim 1 wherein the sealed pouch comprises a heat sealedpouch.
 3. The package of claim 1 wherein the liquid core cathetercomprises a liquid core ablation catheter.
 4. The package assembly ofclaim 1 wherein each end of the polymer spiral tube comprises a straightsection extending away from a spiral portion of the polymer spiral tube.